References References

107

References

1. Fearon ER, Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990;

61: 759-67.

2. Lu X, Lane DP. Differential induction of transcriptionally active p53 following

UV or ionizing radiation: defects in chromosome instability syndromes? Cell.

1993; 75: 765-78.

3. Gowen LC, Avrutskaya AV, Latour AM, Koller BH, Leadon SA. BRCA1 required

for transcription-coupled repair of oxidative DNA damage. Science. 1998; 281:

1009-12.

4. Sharan SK, Morimatsu M, Albrecht U, Lim DS, Regel E, Dinh C, Sands A, Eichele

G,Hasty P, Bradley A. Embryonic lethality and radiation hypersensitivity

mediated by Rad51 in micelacking Brca2. Nature. 1997; 386: 804-10.

5. Fishel R, Lescoe MK, Rao MR, Copeland NG, Jenkins NA, Garber J, Kane M,

Kolodner R. The human mutator gene homolog MSH2 and its association with

hereditary nonpolyposis colon cancer. Cell. 1993; 75: 1027-38.

6. Leach FS, Nicolaides NC, Papadopoulos N, Liu B, Jen J, Parsons R, Peltomaki

P,Sistonen P, Aaltonen LA, Nystrom-Lahti M, et al. Mutations of a mutS

homolog in hereditary nonpolyposis colorectal cancer. Cell. 1993; 75: 1215-25.

7. Bronner CE, Baker SM, Morrison PT, Warren G, Smith LG, Lescoe MK, Kane

M,Earabino C, Lipford J, Lindblom A, et al. Mutation in the DNA mismatch

repair gene homologue hMLH1 is associated with hereditary non-polyposis

colon cancer. Nature. 1994; 368: 258-61.

8. Papadopoulos N, Nicolaides NC, Wei YF, Ruben SM, Carter KC, Rosen CA,

Haseltine WA, Fleischmann RD, Fraser CM, Adams MD, et al. Mutation of a

mutL homolog in hereditary colon cancer. Science. 1994; 263: 1625-9.

9. Ehrlich P.1909. Ueber den jetzigen Stand der Karzinomforschung. Ned.

Tijdschr.Geneeskd. 5(part 1): 273-90.

108

10. Burnet FM. The concept of immunological surveillance. Prog Exp Tumor Res.

1970; 13: 1-27.

11. Burnet FM. Immunological surveillance in neoplasia. Transplant Rev. 1971; 7: 3-

25.

12. Burnet FM. Immunological aspects of malignant disease. Lancet. 1967 Jun 3; 1:

1171-4.

13. Foley EJ. Antigenic properties of methylcholanthrene-induced tumors in mice of

the strain of origin. Cancer Res. 1953; 13: 835-7.

14. Prehn RT, Main JM. Immunity to methylcholanthrene-induced sarcomas. J Natl

Cancer Inst. 1957; 18: 769-78.

15. Old LJ, Boyse EA. Specific antigens of tumors and leukemias of experimental

animals. Med Clin North Am. 1966; 50: 901-12.

16. Klein G. Tumor antigens. Annu Rev Microbiol. 1966; 20: 223-52.

17. Flanagan SP. ʹNudeʹ, a new hairless gene with pleiotropic effects in the

mouse.Genet Res. 1966; 8: 295-309.

18. Pantelouris EM. Absence of thymus in a mouse mutant. Nature. 1968; 217: 370-1.

19. Stutman O. Tumor development after 3-methylcholanthrene in immunologically

deficient athymic-nude mice. Science. 1974; 183: 534-6.

20. Stutman O. Lymphocyte sequestration: its possible role in tumor immunity.

Transplant Proc. 1973; 5: 969-73.

21. Stutman O. Chemical carcinogenesis in nude mice: comparison between nude

mice from homozygous matings and heterozygous matings and effect of age and

carcinogen dose. J Natl Cancer Inst. 1979; 62: 353-8.

22. Rygaard J, Povlsen CO. Is immunological surveillance not a cell-mediated

immune function? Transplantation. 1974; 17: 135-6.

23. Rygaard J, Povlsen CO. The nude mouse vs. the hypothesis of immunological

surveillance. Transplant Rev. 1976; 28: 43-61.

24. Maleckar JR, Sherman LA. The composition of the T cell receptor repertoire in

nude mice. J Immunol. 1987; 138: 3873-6.

109

25. Ikehara S, Pahwa RN, Fernandes G, Hansen CT, Good RA. Functional T cells in

athymic nude mice. Proc Natl Acad Sci U S A. 1984; 81: 886-8.

26. Herberman RB, Holden HT. Natural cell-mediated immunity. Adv Cancer Res.

1978; 27: 305-77.

27. Heidelberger C. Chemical carcinogenesis. Annu Rev Biochem. 1975; 44: 79-121.

28. Penn I. Tumors of the immunocompromised patient. Annu Rev Med. 1988; 39:

63-73.

29. List AF, Greco FA, Vogler LB. Lymphoproliferative diseases in

immunocompromised hosts: the role of Epstein-Barr virus. J Clin Oncol. 1987; 5:

1673-89.

30. Gaidano G, Dalla-Favera R. Biologic aspects of human immunodeficiency virus-

related lymphoma. Curr Opin Oncol. 1992; 4: 900-6.

31. Hanto DW, Birkenbach M, Frizzera G, Gajl-Peczalska KJ, Simmons RL, Schubach

WH. Confirmation of the heterogeneity of post transplant Epstein-Barr virus-

associated B cell proliferations by immunoglobulin gene rearrangement analyses.

Transplantation. 1989; 47: 458-64.

32. Heslop HE, Ng CY, Li C, Smith CA, Loftin SK, Krance RA, Brenner MK, Rooney

CM. Long-term restoration of immunity against Epstein-Barr virus infection by

adoptive transfer of gene-modified virus-specific T lymphocytes. Nat Med. 1996;

2: 551-5.

33. Mesri EA, Cesarman E, Arvanitakis L, Rafii S, Moore MA, Posnett DN, Knowles

DM,Asch AS. Human herpesvirus-8/Kaposiʹs sarcoma-associated herpesvirus is

a new transmissible virus that infects B cells. J Exp Med. 1996; 183: 2385-90.

34. Cesarman E, Mesri EA. Virus-associated lymphomas. Curr Opin Oncol. 1999; 11:

322-32.

35. Boshart M, Gissmann L, Ikenberg H, Kleinheinz A, Scheurlen W, zur Hausen H.

A new type of papillomavirus DNA, its presence in genital cancer biopsies and

in cell lines derived from cervical cancer. EMBO J. 1984; 3: 1151-7.

110

36. Beaudenon S, Kremsdorf D, Croissant O, Jablonska S, Wain-Hobson S, Orth G. A

novel type of human papillomavirus associated with genital neoplasias. Nature.

1986; 321: 246-9.

37. McFarlane GA, Munro A. Helicobacter pylori and gastric cancer. Br J Surg. 1997;

84: 1190-9.

38. Shinkai Y, Rathbun G, Lam KP, Oltz EM, Stewart V, Mendelsohn M, Charron J,

Datta M, Young F, Stall AM, et al. RAG-2-deficient mice lack mature

lymphocytes owing to inability to initiate V(D)J rearrangement. Cell. 1992; 68:

855-67.

39. Smyth MJ, Dunn GP, Schreiber RD. Cancer immunosurveillance and

immunoediting: the roles of immunity in suppressing tumor development and

shaping tumor immunogenicity. Adv Immunol. 2006; 90: 1-50.

40. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby

P,Sutton B, Tigelaar RE, Hayday AC. Regulation of cutaneous malignancy by

gammadelta T cells. Science. 2001; 294: 605-9.

41. Girardi M. Immunosurveillance and immunoregulation by gammadelta T cells. J

Invest Dermatol. 2006; 126: 25-31.

42. Smyth MJ, Crowe NY, Godfrey DI. NK cells and NKT cells collaborate in host

protection from methylcholanthrene-induced fibrosarcoma. Int Immunol. 2001;

13: 459-63.

43. Crowe NY, Smyth MJ, Godfrey DI. A critical role for natural killer T cells in

immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med. 2002;

196: 119-27. 44. Dighe AS, Richards E, Old LJ, Schreiber RD. Enhanced in vivo growth and

resistance to rejection of tumor cells expressing dominant negative IFN gamma

receptors. Immunity. 1994; 1: 447-56.

45. Kaplan DH, Shankaran V, Dighe AS, Stockert E, Aguet M, Old LJ, Schreiber RD.

Demonstration of an interferon gamma-dependent tumor surveillance system in

immunocompetent mice. Proc Natl Acad Sci U S A. 1998; 95: 7556-61.

111

46. Street SE, Cretney E, Smyth MJ. Perforin and interferon-gamma activities

independently control tumor initiation, growth, and metastasis. Blood. 2001; 97:

192-7. 47. Smyth MJ, Thia KY, Street SE, MacGregor D, Godfrey DI, Trapani JA. Perforin-

mediated cytotoxicity is critical for surveillance of spontaneous lymphoma. J Exp

Med. 2000; 192: 755-60. 48. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T,

Pelikan SB, Crowe NY, Godfrey DI. Differential tumor surveillance by natural

killer (NK) and NKT cells.J Exp Med. 2000; 191: 661-8. 49. van den Broek ME, Kagi D, Ossendorp F, Toes R, Vamvakas S, Lutz WK, Melief

CJ, Zinkernagel RM, Hengartner H. Decreased tumor surveillance in perforin-

deficient mice. J Exp Med. 1996; 184: 1781-90.

50. Smyth MJ, Takeda K, Hayakawa Y, Peschon JJ, van den Brink MR, Yagita H.

Natureʹs TRAIL--on a path to cancer immunotherapy. Immunity. 2003; 18: 1-6.

51. Takeda K, Smyth MJ, Cretney E, Hayakawa Y, Yamaguchi N, Yagita H,

Okumura K. Involvement of tumor necrosis factor-related apoptosis-inducing

ligand in NK cell-mediated and IFN-gamma-dependent suppression of

subcutaneous tumor growth. Cell Immunol. 2001; 214: 194-200.

52. Cretney E, Takeda K, Yagita H, Glaccum M, Peschon JJ, Smyth MJ. Increased

susceptibility to tumor initiation and metastasis in TNF-related apoptosis-

inducing ligand-deficient mice. J Immunol. 2002; 168: 1356-61.

53. Penn I. Tumors in allograft recipients. N Engl J Med. 1979; 301: 385.

54. Penn I. Occurrence of cancers in immunosuppressed organ transplant recipients.

Clin Transpl. 1998; 147-58.

55. Penn I. Post-transplant malignancy: the role of immunosuppression. Drug Saf.

2000; 23: 101-13.

56. Good RA, Finstad J. Essential relationship between the lymphoid system,

immunity, and malignancy. Natl Cancer Inst Monogr. 1969; 31: 41-58.

112

57. Gatti RA, Good RA. Occurrence of malignancy in immunodeficiency diseases. A

literature review. Cancer. 1971; 28: 89-98.

58. Kersey JH, Spector BD, Good RA. Primary immunodeficiency diseases and

cancer: the immunodeficiency-cancer registry. Int J Cancer. 1973; 12: 333-47.

59. Boshoff C, Weiss R. AIDS-related malignancies. Nat Rev Cancer. 2002; 2: 373-82.

60. Newton R, Carpenter L, Casabonne D, Beral V, Babiker A, Darbyshire J, Weller

I,Weiss R, Kwan A, Bourboulia D, Munoz F, Lagos D, Boshoff C. A prospective

study of Kaposiʹs sarcoma-associated herpesvirus and Epstein-Barr virus in

adults with human immunodeficiency virus-1. Br J Cancer. 2006; 94: 1504-9.

61. Sheil AG, Disney AP, Mathew TG, Amiss N, Excell L. Malignancy following

renal transplantation. Transplant Proc. 1992; 24: 1946-7.

62. Sheil AG. Organ transplantation and malignancy: inevitable linkage. Transplant

Proc. 2002; 34: 2436-7.

63. Pham SM, Kormos RL, Landreneau RJ, Kawai A, Gonzalez-Cancel I, Hardesty

RL,Hattler BG, Griffith BP. Solid tumors after heart transplantation: lethality of

lung cancer. Ann Thorac Surg. 1995; 60: 1623-6.

64. DeVeale B, Brummel T, Seroude L. Immunity and aging: the enemy within?

Aging Cell. 2004; 3: 195-208.

65. Burns EA, Leventhal EA. Aging, immunity, and cancer. Cancer Control. 2000; 7:

513-22.

66. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000; 100: 57-70.

67. Hanahan D, Folkman J. Patterns and emerging mechanisms of the angiogenic

switch during tumorigenesis. Cell. 1996; 86: 353-64.

68. Carmeliet P, Jain RK. Angiogenesis in cancer and other diseases. Nature. 2000;

407: 249-57.

69. Sternlicht MD, Werb Z. How matrix metalloproteinases regulate cell behavior.

Annu Rev Cell Dev Biol. 2001; 17: 463-516.

70. Vicari AP, Caux C. Chemokines in cancer. Cytokine Growth Factor Rev. 2002; 13:

143-54.

113

71. Matzinger P. Tolerance, danger, and the extended family. Annu Rev Immunol.

1994; 12: 991-1045.

72. Wrenshall LE, Stevens RB, Cerra FB, Platt JL. Modulation of macrophage and B

cell function by glycosaminoglycans. J Leukoc Biol. 1999; 66: 391-400.

73. Hodge-Dufour J, Noble PW, Horton MR, Bao C, Wysoka M, Burdick MD, Strieter

RM, Trinchieri G, Pure E. Induction of IL-12 and chemokines by hyaluronan

requires adhesion-dependent priming of resident but not elicited macrophages. J

Immunol. 1997; 159: 2492-500.

74. Bancroft GJ, Schreiber RD, Unanue ER.Natural immunity: a T-cell-independent

pathway of macrophage activation, defined in the scid mouse. Immunol Rev.

1991; 124: 5-24.

75. Diefenbach A, Jamieson AM, Liu SD, Shastri N, Raulet DH.Ligands for the

murine NKG2D receptor: expression by tumor cells and activation of NK cells

and macrophages. Nat Immunol. 2000; 1: 119-26. 76. Bromberg JF, Horvath CM, Wen Z, Schreiber RD, Darnell JE Jr.Transcriptionally

active Stat1 is required for the antiproliferative effects of both interferon alpha

and interferon gamma. Proc Natl Acad Sci U S A. 1996; 93: 7673-8.

77. Luster AD, Leder P. IP-10, a -C-X-C- chemokine, elicits a potent thymus-

dependent antitumor response in vivo. J Exp Med. 1993; 178: 1057-65.

78. Coughlin CM, Salhany KE, Gee MS, LaTemple DC, Kotenko S, Ma X, Gri G,

Wysocka M,Kim JE, Liu L, Liao F, Farber JM, Pestka S, Trinchieri G, Lee WM.

Tumor cell responses to IFN-γ affect tumorigenicity and response to IL-12

therapy and antiangiogenesis. Immunity. 1998; 9: 25-34.

79. Qin Z, Blankenstein T. CD4+ T cell--mediated tumor rejection involves inhibition

of angiogenesis that is dependent on IFN gamma receptor expression by non

hematopoietic cells. Immunity. 2000; 12: 677-86.

80. Pace JL, Russell SW, Schreiber RD, Altman A, Katz DH. Macrophage activation:

priming activity from a T-cell hybridoma is attributable to interferon-gamma.

Proc Natl Acad Sci U S A. 1983; 80: 3782-6.

114

81. Nathan CF, Murray HW, Wiebe ME, Rubin BY. Identification of interferon-

gamma as the lymphokine that activates human macrophage oxidative

metabolism and antimicrobial activity. J Exp Med. 1983; 158: 670-89.

82. MacMicking J, Xie QW, Nathan C. Nitric oxide and macrophage function. Annu

Rev Immunol. 1997; 15: 323-50.

83. Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G.

Reciprocal activating interaction between natural killer cells and dendritic cells. J

Exp Med. 2002; 195: 327-33.

84. Srivastava P. Interaction of heat shock proteins with peptides and antigen

presenting cells:chaperoning of the innate and adaptive immune responses.

Annu Rev Immunol. 2002; 20: 395-425.

85. Sallusto F, Mackay CR, Lanzavecchia A. The role of chemokine receptors in

primary, effector, and memory immune responses. Annu Rev Immunol. 2000; 18:

593-620.

86. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role

of bone marrow-derived cells in presenting MHC class I-restricted tumor

antigens. Science. 1994; 264: 961-5.

87. Herberman RB, Nunn ME, Holden HT, Lavrin DH. Natural cytotoxic reactivity

of mouse lymphoid cells against syngeneic and allogeneic tumors. II.

Characterization of effector cells. Int J Cancer. 1975; 16: 230-9.

88. Herberman RB, Nunn ME, Lavrin DH. Natural cytotoxic reactivity of mouse

lymphoid cells against syngeneic acid allogeneic tumors. I. Distribution of

reactivity and specificity. Int J Cancer. 1975; 16: 216-29.

89. Karre K, Klein GO, Kiessling R, Klein G, Roder JC. In vitro NK-activity and in

vivo resistance to leukemia: studies of beige,beige//nude and wild-type hosts on

C57BL background. Int J Cancer. 1980; 26: 789-97.

90. Talmadge JE, Meyers KM, Prieur DJ, Starkey JR. Role of NK cells in tumour

growth and metastasis in beige mice. Nature. 1980; 284: 622-4.

115

91. van den Broek MF, Kagi D, Zinkernagel RM, Hengartner H. Perforin dependence

of natural killer cell-mediated tumor control in vivo. Eur J Immunol. 1995; 25:

3514-6.

92. Piontek GE, Taniguchi K, Ljunggren HG, Gronberg A, Kiessling R, Klein G,

Karre K. YAC-1 MHC class I variants reveal an association between decreased

NK sensitivity and increased H-2 expression after interferon treatment or in vivo

passage. J Immunol. 1985; 135: 4281-8.

93. Karre K, Ljunggren HG, Piontek G, Kiessling R.Selective rejection of H-2-

deficient lymphoma variants suggests alternative immune defence strategy.

Nature. 1986; 319: 675-8.

94. Ljunggren HG, Sturmhofel K, Wolpert E, Hammerling GJ, Karre K. Transfection

of beta 2-microglobulin restores IFN-mediated protection from natural killer cell

lysis in YAC-1 lymphoma variants. J Immunol. 1990; 145: 380-6.

95. Franksson L, George E, Powis S, Butcher G, Howard J, Karre K. Tumorigenicity

conferred to lymphoma mutant by major histocompatibility complex-encoded

transporter gene. J Exp Med. 1993; 177: 201-5.

96. Garrido F, Cabrera T, Lopez-Nevot MA, Ruiz-Cabello F. HLA class I antigens in

human tumors. Adv Cancer Res. 1995; 67: 155-95.

97. Yokoyama WM, Jacobs LB, Kanagawa O, Shevach EM, Cohen DI. A murine T

lymphocyte antigen belongs to a supergene family of type II integral membrane

proteins. J Immunol. 1989; 143: 1379-86.

98. Chan PY, Takei F. Molecular cloning and characterization of a novel murine T

cell surface antigen, YE1/48. J Immunol. 1989; 142: 1727-36.

99. Karlhofer FM, Ribaudo RK, Yokoyama WM. MHC class I alloantigen specificity

of Ly-49+ IL-2-activated natural killer cells. Nature. 1992; 358: 66-70.

100. Colonna M, Samaridis J. Cloning of immunoglobulin-superfamily members

associated with HLA-C and HLA-B recognition by human natural killer cells.

Science. 1995; 268: 405-8.

116

101. Lazetic S, Chang C, Houchins JP, Lanier LL, Phillips JH. Human natural killer

cell receptors involved in MHC class I recognition are disulfide-linked

heterodimers of CD94 and NKG2 subunits. J Immunol. 1996; 157: 4741-5.

102. Carretero M, Cantoni C, Bellon T, Bottino C, Biassoni R, Rodriguez A,Perez-

Villar JJ, Moretta L, Moretta A, Lopez-Botet M. The CD94 and NKG2-A C-type

lectins covalently assemble to form a natural killer cell inhibitory receptor for

HLA class I molecules. Eur J Immunol. 1997; 27: 563-7.

103. Vance RE, Tanamachi DM, Hanke T, Raulet DH. Cloning of a mouse homolog

of CD94 extends the family of C-type lectins on murine natural killer cells. Eur

J Immunol. 1997; 27: 3236-41.

104. Moretta A, Vitale M, Bottino C, Orengo AM, Morelli L, Augugliaro R, Barbaresi

M,Ciccone E, Moretta L. P58 molecules as putative receptors for major

histocompatibility complex (MHC)class I molecules in human natural killer

(NK) cells. Anti-p58 antibodies reconstitute lysis of MHC class I-protected cells

in NK clones displaying different specificities. J Exp Med. 1993; 178: 597-604.

105. Wagtmann N, Rajagopalan S, Winter CC, Peruzzi M, Long EO. Killer cell

inhibitory receptors specific for HLA-C and HLA-B identified by direct binding

and by functional transfer. Immunity. 1995; 3: 801-9.

106. Vance RE, Kraft JR, Altman JD, Jensen PE, Raulet DH. Mouse CD94/NKG2A is

a natural killer cell receptor for the nonclassical major histocompatibility

complex (MHC) class I molecule Qa-1(b. J Exp Med. 1998; 188: 1841-8.

107. Braud VM, Allan DS, OʹCallaghan CA, Soderstrom K, DʹAndrea A, Ogg GS,

Lazetic S, Young NT, Bell JI, Phillips JH, Lanier LL, McMichael AJ. HLA-E

binds to natural killer cell receptors CD94/NKG2A, B and C. Nature. 1998; 391:

795-9.

108. Vance RE, Jamieson AM, Raulet DH. Recognition of the class Ib molecule Qa-

1(b) by putative activating receptors CD94/NKG2C and CD94/NKG2E on

mouse natural killer cells. J Exp Med. 1999; 190: 1801-12.

117

109. Raulet DH, Vance RE, McMahon CW. Regulation of the natural killer cell

receptor repertoire. Annu Rev Immunol. 2001; 19: 291-330.

110. Bix M, Liao NS, Zijlstra M, Loring J, Jaenisch R, Raulet D. Rejection of class I

MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature.

1991; 349: 329-31.

111. Ljunggren HG, Karre K. In search of the ʹmissing selfʹ: MHC molecules and NK

cell recognition. Immunol Today. 1990; 11: 237-44.

112. Hoglund P, Ohlen C, Carbone E, Franksson L, Ljunggren HG, Latour A, Koller

B, Karre K. Recognition of beta 2-microglobulin-negative (beta 2m-) T-cell

blasts by natural killer cells from normal but not from beta 2m- mice:

nonresponsiveness controlled by beta 2m- bone marrow in chimeric mice. Proc

Natl Acad Sci U S A. 1991; 88: 10332-6.

113. Bix M, Liao NS, Zijlstra M, Loring J, Jaenisch R, Raulet D. Rejection of class I

MHC-deficient haemopoietic cells by irradiated MHC-matched mice. Nature.

1991; 349: 329-31.

114. Lanier LL, Corliss B, Phillips JH. Arousal and inhibition of human NK cells.

Immunol Rev. 1997; 155: 145-54.

115. Diefenbach A, Jensen ER, Jamieson AM, Raulet DH. Rae1 and H60 ligands of

the NKG2D receptor stimulate tumour immunity. Nature. 2001; 413: 165-71.

116. Cerwenka A, Baron JL, Lanier LL. Ectopic expression of retinoic acid early

inducible-1 gene (RAE-1) permits natural killer cell-mediated rejection of a

MHC class I-bearing tumor in vivo. Proc Natl Acad Sci U S A. 2001; 98: 11521-6.

117. Leiden JM, Karpinski BA, Gottschalk L, Kornbluth J. Susceptibility to natural

killer cell-mediated cytolysis is independent of the level of target cell class I

HLA expression. J Immunol. 1989; 142: 2140-7.

118. Nishimura MI, Stroynowski I, Hood L, Ostrand-Rosenberg S. H-2Kb antigen

expression has no effect on natural killer susceptibility and tumorigenicity of a

murine hepatoma. J Immunol. 1988; 141: 4403-9.

118

119. Pena J, Alonso C, Solana R, Serrano R, Carracedo J, Ramirez R. Natural killer

susceptibility is independent of HLA class I antigen expression on cell lines

obtained from human solid tumors. Eur J Immunol. 1990; 20: 2445-8.

120. Litwin V, Gumperz J, Parham P, Phillips JH, Lanier LL. Specificity of HLA class

I antigen recognition by human NK clones: evidence for clonal heterogeneity,

protection by self and non-self alleles, and influence of the target cell type. J

Exp Med. 1993; 178: 1321-36.

121. Ryan JC, Niemi EC, Nakamura MC, Seaman WE. NKR-P1A is a target-specific

receptor that activates natural killer cell cytotoxicity. J Exp Med. 1995; 181:

1911-5.

122. Diefenbach A, Jamieson AM, Liu SD, Shastri N, Raulet DH. Ligands for the

murine NKG2D receptor: expression by tumor cells and activation of NK cells

and macrophages. Nat Immunol. 2000; 1: 119-26.

123. Ho EL, Heusel JW, Brown MG, Matsumoto K, Scalzo AA, Yokoyama WM.

Murine Nkg2d and Cd94 are clustered within the natural killer complex and

are expressed independently in natural killer cells. Proc Natl Acad Sci U S A.

1998; 95: 6320-5.

124. Wu J, Song Y, Bakker AB, Bauer S, Spies T, Lanier LL, Phillips JH. An

activating immunoreceptor complex formed by NKG2D and DAP10.Science.

1999; 285: 730-2.

125. Chang C, Dietrich J, Harpur AG, Lindquist JA, Haude A, Loke YW, King A,

Colonna M, Trowsdale J, Wilson MJ. Cutting edge: KAP10, a novel

transmembrane adapter protein genetically linked to DAP12 but with unique

signaling properties. J Immunol. 1999; 163: 4651-4.

126. Wu J, Cherwinski H, Spies T, Phillips JH, Lanier LL. DAP10 and DAP12 form

distinct, but functionally cooperative, receptor complexes in natural killer cells.

J Exp Med. 2000; 192: 1059-68.

127. Bendelac A, Rivera MN, Park SH, Roark JH. Mouse CD1-specific NK1 T cells:

development, specificity, and function. Annu Rev Immunol. 1997; 15: 535-62.

119

128. Godfrey DI, MacDonald HR, Kronenberg M, Smyth MJ, Van Kaer L. NKT cells:

whatʹs in a name? Nat Rev Immunol. 2004; 4: 231-7.

129. Exley MA, He Q, Cheng O, Wang RJ, Cheney CP, Balk SP, Koziel MJ. Cutting

edge: Compartmentalization of Th1-like noninvariant CD1d-reactive T cells in

hepatitis C virus-infected liver. J Immunol. 2002; 68: 1519-23.

130. Exley MA, Tahir SM, Cheng O, Shaulov A, Joyce R, Avigan D, Sackstein R,

Balk SP.A major fraction of human bone marrow lymphocytes are Th2-like

CD1d-reactive T cells that can suppress mixed lymphocyte responses.

Immunol. 2001; 167: 5531-4.

131. Behar SM, Podrebarac TA, Roy CJ, Wang CR, Brenner MB. Diverse TCRs

recognize murine CD1. J Immunol. 1999; 162: 161-7.

132. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano

T,Pelikan SB, Crowe NY, Godfrey DI. Differential tumor surveillance by

natural killer (NK) and NKT cells. J Exp Med. 2000; 191: 661-8.

133. Crowe NY, Smyth MJ, Godfrey DI. A critical role for natural killer T cells in

immunosurveillance of methylcholanthrene-induced sarcomas. J Exp Med.

2002; 196: 119-27.

134. Swann J, Crowe NY, Hayakawa Y, Godfrey DI, Smyth MJ. Regulation of

antitumour immunity by CD1d-restricted NKT cells. Immunol Cell Biol. 2004;

82: 323-31.

135. Stewart TJ, Smyth MJ, Fernando GJ, Frazer IH, Leggatt GR. Inhibition of early

tumor growth requires J alpha 18-positive (natural killer T) cells. Cancer Res.

2003; 63: 3058-60.

136. Kawano T, Nakayama T, Kamada N, Kaneko Y, Harada M, Ogura N, Akutsu

Y, Motohashi S, Iizasa T, Endo H, Fujisawa T, Shinkai H, Taniguchi M.

Antitumor cytotoxicity mediated by ligand-activated human V alpha24 NKT

cells. Cancer Res. 1999; 59: 5102-5.

137. Motohashi S, Kobayashi S, Ito T, Magara KK, Mikuni O, Kamada N, Iizasa T,

Nakayama T, Fujisawa T, Taniguchi M. Preserved IFN-α production of

120

circulating Valpha24 NKT cells in primary lung cancer patients. Int J Cancer.

2002; 102: 159-65.

138. Boismenu R, Havran WL. An innate view of gamma delta T cells. Curr Opin

Immunol. 1997; 9: 57-63.

139. Girardi M. Immunosurveillance and immunoregulation by gammadelta T cells.

J Invest Dermatol. 2006; 126: 25-31.

140. Born WK, Reardon CL, OʹBrien RL. The function of gammadelta T cells in

innate immunity. Curr Opin Immunol. 2006; 18: 31-8.

141. Zocchi MR, Poggi A. Role of gammadelta T lymphocytes in tumor defense.

Front Biosci. 2004; 9: 2588-604.

142. Ferrarini M, Ferrero E, Dagna L, Poggi A, Zocchi MR. Human gammadelta T

cells: a nonredundant system in the immune-surveillance against cancer.

Trends Immunol. 2002; 23: 14-8.

143. Ensslin AS, Formby B. Comparison of cytolytic and proliferative activities of

human gamma delta and alpha beta T cells from peripheral blood against

various human tumor cell lines. J Natl Cancer Inst. 1991; 83: 1564-9.

144. Hayday AC. Gamma delta cells: a right time and a right place for a conserved

third way of protection. Annu Rev Immunol. 2000; 18: 975-1026.

145. Bauer S, Groh V, Wu J, Steinle A, Phillips JH, Lanier LL, Spies T. Activation of

NK cells and T cells by NKG2D, a receptor for stress-inducible MICA. Science.

1999; 285: 727-9.

146. Cerwenka A, Bakker AB, McClanahan T, Wagner J, Wu J, Phillips JH, Lanier

LL. Retinoic acid early inducible genes define a ligand family for the activating

NKG2D receptor in mice. Immunity. 2000; 12: 721-7. 147. Girardi M, Oppenheim DE, Steele CR, Lewis JM, Glusac E, Filler R, Hobby P,

Sutton B, Tigelaar RE, Hayday AC. Regulation of cutaneous malignancy by

gammadelta T cells. Science. 2001; 294: 605-9.

121

148. Ferrarini M, Pupa SM, Zocchi MR, Rugarli C, Menard S. Distinct pattern of

HSP72 and monomeric laminin receptor expression in human lung cancers

infiltrated by gamma/delta T lymphocytes. Int J Cancer. 1994; 57: 486-90.

149. Zocchi MR, Ferrarini M, Rugarli C. Selective lysis of the autologous tumor by

delta TCS1+ gamma/delta+ tumor-infiltrating lymphocytes from human lung

carcinomas. Eur J Immunol. 1990; 20: 2685-9.

150. Choudhary A, Davodeau F, Moreau A, Peyrat MA, Bonneville M, Jotereau F.

Selective lysis of autologous tumor cells by recurrent gamma delta tumor-

infiltrating lymphocytes from renal carcinoma. J Immunol. 1995; 154: 3932-40.

151. Zhao X, Wei YQ, Kariya Y, Teshigawara K, Uchida A. Accumulation of

gamma/delta T cells in human dysgerminoma and seminoma: roles in

autologous tumor killing and granuloma formation.Immunol Invest. 1995; 24:

607-18.

152. Arden B, Clark SP, Kabelitz D, Mak TW. Human T-cell receptor variable gene

segment families. Immunogenetics. 1995; 42: 455-500.

153. Fu YX, Vollmer M, Kalataradi H, Heyborne K, Reardon C, Miles C, OʹBrien R,

Born W. Structural requirements for peptides that stimulate a subset of gamma

delta T cells. J Immunol. 1994; 152: 1578-88.

154. Laad AD, Thomas ML, Fakih AR, Chiplunkar SV. Human gamma delta T cells

recognize heat shock protein-60 on oral tumor cells. Int J Cancer. 1999; 80: 709-

14.

155. Wright A, Lee JE, Link MP, Smith SD, Carroll W, Levy R, Clayberger C,

Krensky AM. Cytotoxic T lymphocytes specific for self tumor immunoglobulin

express T cell receptor delta chain. J Exp Med. 1989; 169: 1557-64.

156. Freedman MS, DʹSouza S, Antel JP. γ δ T-cell-human glial cell interactions. I. In

vitro induction of γδ T-cell expansion by human glial cells. J Neuroimmunol.

1997; 74: 135-42.

122

157. Kunzmann V, Bauer E, Feurle J, Weissinger F, Tony HP, Wilhelm M.

Stimulation of gammadelta T cells by aminobisphosphonates and induction of

antiplasma cell activity in multiple myeloma. Blood. 2000; 96: 384-92.

158. Schilbach KE, Geiselhart A, Wessels JT, Niethammer D, Handgretinger R.

Human gamma delta T lymphocytes exert natural and IL-2-induced

cytotoxicity to neuroblastoma cells. J Immunother. 2000; 23: 536-48.

159. Leca G, Vita N, Maiza H, Fasseu M, Bensussan A. A monoclonal antibody to

the Hodgkinʹs disease-associated antigen CD30 induces activation and long-

term growth of human autoreactive gamma delta T cell clone. Cell Immunol.

1994; 156: 230-9.

160. Maccario R, Revello MG, Comoli P, Montagna D, Locatelli F, Gerna G. HLA-

unrestricted killing of HSV-1-infected mononuclear cells. Involvement of either

gamma/delta+ or alpha/beta+ human cytotoxic T lymphocytes. J Immunol.

1993; 150: 1437-45. 161. Gao Y, Yang W, Pan M, Scully E, Girardi M, Augenlicht LH, Craft J, Yin Z.

Gamma delta T cells provide an early source of interferon gamma in tumor

immunity. J Exp Med. 2003; 198: 433-42.

162. Cammarota G, Scheirle A, Takacs B, Doran DM, Knorr R, Bannwarth W,

Guardiola J, Sinigaglia F. Identification of a CD4 binding site on the beta 2

domain of HLA-DR molecules. Nature. 1992; 356: 799-801.

163. Potter TA, Rajan TV, Dick RF 2nd, Bluestone JA. Substitution at residue 227 of

H-2 class I molecules abrogates recognition by CD8-dependent, but not CD8-

independent, cytotoxic T lymphocytes. Nature. 1989; 337: 73-5.

164. Pardoll DM, Topalian SL. The role of CD4+ T cell responses in antitumor

immunity. Curr Opin Immunol. 1998; 10: 588-94.

165. Mumberg D, Monach PA, Wanderling S, Philip M, Toledano AY, Schreiber RD,

Schreiber H. CD4(+) T cells eliminate MHC class II-negative cancer cells in vivo

by indirect effects of IFN-gamma. Proc Natl Acad Sci U S A. 1999; 96: 8633-8.

123

166. Greenberg PD, Cheever MA, Fefer A. Eradication of disseminated murine

leukemia by chemoimmunotherapy with cyclophosphamide and adoptively

transferred immune syngeneic Lyt-1+2-lymphocytes. J Exp Med. 1981; 154: 952-

63.

167. Fujiwara H, Fukuzawa M, Yoshioka T, Nakajima H, Hamaoka T. The role of

tumor-specific Lyt-1+2- T cells in eradicating tumor cells in vivo. I. Lyt-1+2- T

cells do not necessarily require recruitment of hostʹs cytotoxic T cell precursors

for implementation of in vivo immunity. J Immunol. 1984; 133: 1671-6.

168. Monach PA, Meredith SC, Siegel CT, Schreiber H. A unique tumor antigen

produced by a single amino acid substitution. Immunity. 1995; 2: 45-59.

169. Beatty GL, Paterson Y. IFN-gamma can promote tumor evasion of the immune

system in vivo by down-regulating cellular levels of an endogenous tumor

antigen. J Immunol. 2000; 165: 5502-8.

170. Huang AY, Bruce AT, Pardoll DM, Levitsky HI. In vivo cross-priming of MHC

class I-restricted antigens requires the TAP transporter. Immunity. 1996; 4: 349-

55.

171. Huang AY, Golumbek P, Ahmadzadeh M, Jaffee E, Pardoll D, Levitsky H. Role

of bone marrow-derived cells in presenting MHC class I-restricted tumor

antigens. Science. 1994; 264: 961-5.

172. Toes RE, Ossendorp F, Offringa R, Melief CJ. CD4 T cells and their role in

antitumor immune responses. J Exp Med. 1999; 189: 753-6.

173. Bennett SR, Carbone FR, Karamalis F, Miller JF, Heath WR. Induction of a

CD8+ cytotoxic T lymphocyte response by cross-priming requires cognate

CD4+ T cell help. J Exp Med. 1997; 186: 65-70.

174. Ridge JP, Di Rosa F, Matzinger P. A conditioned dendritic cell can be a

temporal bridge between a CD4+ T-helper and a T-killer cell. Nature. 1998; 393:

474-8.

175. Greenberg PD. Adoptive T cell therapy of tumors: mechanisms operative in the

recognition and elimination of tumor cells. Adv Immunol. 1991; 49: 281-355.

124

176. Tite JP, Janeway CA Jr. Antigen-dependent selection of B lymphoma cells

varying in Ia density by cloned antigen-specific L3T4a+ T cells: a possible in

vitro model for B cell adaptive differentiation. J Mol Cell Immunol. 1984; 1: 253-

65.

177. Ozaki S, York-Jolley J, Kawamura H, Berzofsky JA. Cloned protein antigen-

specific, Ia-restricted T cells with both helper and cytolytic activities:

mechanisms of activation and killing. Cell Immunol. 1987; 105: 301-16.

178. Yoshimura A, Shiku H, Nakayama E. Rejection of an IA+ variant line of FBL-3

leukemia by cytotoxic T lymphocytes with CD4+ and CD4-CD8- T cell

receptor-alpha beta phenotypes generated in CD8-depleted C57BL/6 mice. J

Immunol. 1993; 150: 4900-10.

179. Echchakir H, Bagot M, Dorothee G, Martinvalet D, Le Gouvello S, Boumsell L,

Chouaib S, Bensussan A, Mami-Chouaib F. Cutaneous T cell lymphoma

reactive CD4+ cytotoxic T lymphocyte clones display a Th1 cytokine profile

and use a fas-independent pathway for specific tumor cell lysis. J Invest

Dermatol. 2000; 115: 74-80. 180. Nakao M, Sata M, Saitsu H, Yutani S, Kawamoto M, Kojiro M, Itoh K. CD4+

hepatic cancer-specific cytotoxic T lymphocytes in patients with hepatocellular

carcinoma. Cell Immunol. 1997; 177: 176-81.

181. Okada K, Yasumura S, Muller-Fleckenstein I, Fleckenstein B, Talib S,

Koldovsky U, Whiteside TL. Interactions between autologous CD4+ and CD8+

T lymphocytes and human squamous cell carcinoma of the head and neck. Cell

Immunol. 1997; 177: 35-48.

182. Old LJ. Immunotherapy for cancer. Sci Am. 1996; 275: 136-43.

183. Glennie MJ, Johnson PW. Clinical trials of antibody therapy. Immunol Today.

2000; 21: 403-10. 184. Bright RK, Shearer MH, Kennedy RC. Immunization of BALB/c mice with

recombinant simian virus 40 large tumor antigen induces antibody-dependent

125

cell-mediated cytotoxicity against simian virus 40-transformed cells. An

antibody-based mechanism for tumor immunity. J Immunol. 1994; 153: 2064-71. 185. Sliwkowski MX, Lofgren JA, Lewis GD, Hotaling TE, Fendly BM, Fox JA.

Nonclinical studies addressing the mechanism of action of trastuzumab

(Herceptin). Semin Oncol. 1999; 26: 60-70.

186. Clynes RA, Towers TL, Presta LG, Ravetch JV. Inhibitory Fc receptors

modulate in vivo cytotoxicity against tumor targets. Nat Med. 2000; 6: 443-6.

187. Klapper LN, Waterman H, Sela M, Yarden Y. Tumor-inhibitory antibodies to

HER-2/ErbB-2 may act by recruiting c-Cbl and enhancing ubiquitination of

HER-2. Cancer Res. 2000; 60: 3384-8.

188. Reilly RT, Machiels JP, Emens LA, Ercolini AM, Okoye FI, Lei RY, Weintraub

D, Jaffee EM. The collaboration of both humoral and cellular HER-2/neu-

targeted immune responses is required for the complete eradication of HER-

2/neu-expressing tumors. Cancer Res. 2001; 61: 880-3. 189. Folkman J. Antiangiogenic gene therapy. Proc Natl Acad Sci U S A. 1998; 95:

9064-6.

190. Boehm U, Klamp T, Groot M, Howard JC. Cellular responses to interferon-

gamma. Annu Rev Immunol. 1997; 15: 749-95. 191. Hock H, Dorsch M, Diamantstein T, Blankenstein T. Interleukin 7 induces

CD4+ T cell-dependent tumor rejection. J Exp Med. 1991; 174: 1291-8. 192. Levitsky HI, Lazenby A, Hayashi RJ, Pardoll DM. In vivo priming of two

distinct antitumor effector populations: the role of MHC class I expression. J

Exp Med. 1994; 179: 1215-24. 193. Romagnani S. The Th1/Th2 paradigm. Immunol Today. 1997; 18: 263-6.

194. Tsung K, Meko JB, Peplinski GR, Tsung YL, Norton JA. IL-12 induces T helper

1-directed antitumor response. J Immunol. 1997; 158: 3359-65.

195. Aruga A, Aruga E, Tanigawa K, Bishop DK, Sondak VK, Chang AE. Type 1

versus type 2 cytokine release by Vbeta T cell subpopulations determines in

126

vivo antitumor reactivity: IL-10 mediates a suppressive role. J Immunol. 1997;

159: 664-73.

196. Lowes MA, Bishop GA, Crotty K, Barnetson RS, Halliday GM. T helper 1

cytokine mRNA is increased in spontaneously regressing primary melanomas.

J Invest Dermatol. 1997; 108: 914-9.

197. Fallarino F, Gajewski TF. Cutting edge: differentiation of antitumor CTL in

vivo requires host expression of Stat1. J Immunol. 1999; 163: 4109-13. 198. Kacha AK, Fallarino F, Markiewicz MA, Gajewski TF. Cutting edge:

spontaneous rejection of poorly immunogenic P1. HTR tumors by Stat6-

deficient mice. J Immunol. 2000; 165: 6024-8. 199. Kobayashi M, Kobayashi H, Pollard RB, Suzuki F. A pathogenic role of Th2

cells and their cytokine products on the pulmonary metastasis of murine B16

melanoma. J Immunol. 1998; 160: 5869-73. 200. Ostrand-Rosenberg S, Grusby MJ, Clements VK. Cutting edge: STAT6-deficient

mice have enhanced tumor immunity to primary and metastatic mammary

carcinoma. J Immunol. 2000; 165: 6015-9. 201. Pellegrini P, Berghella AM, Del Beato T, Cicia S, Adorno D, Casciani CU.

Disregulation in TH1 and TH2 subsets of CD4+ T cells in peripheral blood of

colorectal cancer patients and involvement in cancer establishment and

progression. Cancer Immunol Immunother. 1996; 42: 1-8.

202. Hu HM, Urba WJ, Fox BA. Gene-modified tumor vaccine with therapeutic

potential shifts tumor-specific T cell response from a type 2 to a type 1 cytokine

profile. J Immunol. 1998; 161: 3033-41.

203. Fearon ER, Pardoll DM, Itaya T, Golumbek P, Levitsky HI, Simons JW,

Karasuyama H, Vogelstein B, Frost P. Interleukin-2 production by tumor cells

bypasses T helper function in the generation of an antitumor response. Cell.

1990; 60: 397-403.

204. Nishimura T, Iwakabe K, Sekimoto M, Ohmi Y, Yahata T, Nakui M, Sato T,

Habu S,Tashiro H, Sato M, Ohta A. Distinct role of antigen-specific T helper

127

type 1 (Th1) and Th2 cells in tumor eradication in vivo. J Exp Med. 1999; 190:

617-27. 205. Hung K, Hayashi R, Lafond-Walker A, Lowenstein C, Pardoll D, Levitsky H.

The central role of CD4(+) T cells in the antitumor immune response. J Exp

Med. 1998; 188: 2357-68. 206. Nakajima C, Uekusa Y, Iwasaki M, Yamaguchi N, Mukai T, Gao P, Tomura M,

Ono S,Tsujimura T, Fujiwara H, Hamaoka T. A role of interferon-gamma (IFN-

gamma) in tumor immunity: T cells with the capacity to reject tumor cells are

generated but fail to migrate to tumor sites in IFN-gamma-deficient mice.

Cancer Res. 2001; 61: 3399-405.

207. Sgadari C, Angiolillo AL, Tosato G. Inhibition of angiogenesis by interleukin-

12 is mediated by the interferon-inducible protein 10. Blood. 1996; 87: 3877-82.

208. Dighe AS, Richards E, Old LJ, Schreiber RD. Enhanced in vivo growth and

resistance to rejection of tumor cells expressing dominant negative IFN gamma

receptors. Immunity. 1994; 1: 447-56.

209. Sauty A, Dziejman M, Taha RA, Iarossi AS, Neote K, Garcia-Zepeda EA,

Hamid Q,Luster AD. The T cell-specific CXC chemokines IP-10, Mig, and I-

TAC are expressed by activated human bronchial epithelial cells. J Immunol.

1999; 162: 3549-58.

210. Angiolillo AL, Sgadari C, Tosato G. A role for the interferon-inducible protein

10 in inhibition of angiogenesis by interleukin-12. Ann N Y Acad Sci. 1996; 795:

158-67.

211. Wigginton JM, Gruys E, Geiselhart L, Subleski J, Komschlies KL, Park JW,

Wiltrout TA, Nagashima K, Back TC, Wiltrout RH. IFN-gamma and Fas/FasL

are required for the antitumor and antiangiogenic effects of IL-12/pulse IL-2

therapy. J Clin Invest. 2001; 108: 51-62.

212. Zinkernagel RM, Doherty PC. Restriction of in vitro T cell-mediated

cytotoxicity in lymphocytic choriomeningitis within a syngeneic or

semiallogeneic system. Nature. 1974; 248: 701-2.

128

213. Zinkernagel RM, Althage A. Antiviral protection by virus-immune cytotoxic T

cells: infected target cells are lysed before infectious virus progeny is

assembled. J Exp Med. 1977; 145: 644-51.

214. Ahmed R, Gray D. Immunological memory and protective immunity:

understanding their relation. Science. 1996; 272: 54-60.

215. Trambas CM, Griffiths GM. Delivering the kiss of death. Nat Immunol. 2003; 4:

399-403.

216. Trapani JA. Dual mechanisms of apoptosis induction by cytotoxic

lymphocytes. Int Rev Cytol. 1998; 182: 111-92.

217. Apasov S, Redegeld F, Sitkovsky M. Cell-mediated cytotoxicity: contact and

secreted factors. Curr Opin Immunol. 1993; 5: 404-10.

218. Contini P, Ghio M, Merlo A, Poggi A, Indiveri F, Puppo F. Apoptosis of

antigen-specific T lymphocytes upon the engagement of CD8 by soluble HLA

class I molecules is Fas ligand/Fas mediated: evidence for the involvement of

p56lck, calcium calmodulin kinase II, and Calcium-independent protein kinase

C signaling pathways and for NF-kappaB and NF-AT nuclear translocation. J

Immunol. 2005; 175: 7244-54.

219. Kajino K, Kajino Y, Greene MI. Fas- and perforin-independent mechanism of

cytotoxic T lymphocyte. Immunol Res. 1998; 17: 89-93.

220. Duke RC, Persechini PM, Chang S, Liu CC, Cohen JJ, Young JD. Purified

perforin induces target cell lysis but not DNA fragmentation. J Exp Med. 1989;

170: 1451-6.

221. Tschopp J, Schafer S, Masson D, Peitsch MC, Heusser C. Phosphorylcholine

acts as a Ca2+-dependent receptor molecule for lymphocyte perforin. Nature.

1989; 337: 272-4.

222. Browne KA, Blink E, Sutton VR, Froelich CJ, Jans DA, Trapani JA. Cytosolic

delivery of granzyme B by bacterial toxins: evidence that endosomal

disruption, in addition to transmembrane pore formation, is an important

function of perforin. Mol Cell Biol. 1999; 19: 8604-15.

129

223. Muller C, Tschopp J. Resistance of CTL to perforin-mediated lysis. Evidence for

a lymphocyte membrane protein interacting with perforin. J Immunol. 1994;

153: 2470-8.

224. Berthou C, Bourge JF, Zhang Y, Soulie A, Geromin D, Denizot Y, Sigaux F,

Sasportes M. Interferon-gamma-induced membrane PAF-receptor expression

confers tumor cell susceptibility to NK perforin-dependent lysis. Blood. 2000;

95: 2329-36.

225. Podack ER. How to induce involuntary suicide: the need for dipeptidyl

peptidase I. Proc Natl Acad Sci U S A. 1999; 96: 8312-4.

226. Froelich CJ, Orth K, Turbov J, Seth P, Gottlieb R, Babior B, Shah GM, Bleackley

RC, Dixit VM, Hanna W. New paradigm for lymphocyte granule-mediated

cytotoxicity. Target cells bind and internalize granzyme B, but an

endosomolytic agent is necessary for cytosolic delivery and subsequent

apoptosis. J Biol Chem. 1996; 271: 29073-9.

227. Shi L, Mai S, Israels S, Browne K, Trapani JA, Greenberg AH. Granzyme B

(GraB) autonomously crosses the cell membrane and perforin initiates

apoptosis and GraB nuclear localization. J Exp Med. 1997; 185: 855-66.

228. Russell JH, Ley TJ. Lymphocyte-mediated cytotoxicity. Annu Rev Immunol.

2002; 20: 323-70.

229. Metkar SS, Wang B, Ebbs ML, Kim JH, Lee YJ, Raja SM, Froelich CJ. Granzyme

B activates procaspase-3 which signals a mitochondrial amplification loop for

maximal apoptosis. J Cell Biol. 2003; 160: 875-85.

230. Yang X, Stennicke HR, Wang B, Green DR, Janicke RU, Srinivasan A, Seth P,

Salvesen GS, Froelich CJ. Granzyme B mimics apical caspases. Description of a

unified pathway for trans-activation of executioner caspase-3 and -7. J Biol

Chem. 1998; 273: 34278-83.

231. Talanian RV, Yang X, Turbov J, Seth P, Ghayur T, Casiano CA, Orth K, Froelich

CJ. Granule-mediated killing: pathways for granzyme B-initiated apoptosis.J

Exp Med. 1997; 186: 1323-31.

130

232. Shi L, Chen G, MacDonald G, Bergeron L, Li H, Miura M, Rotello RJ, Miller

DK, Li P, Seshadri T, Yuan J, Greenberg AH. Activation of an interleukin 1

converting enzyme-dependent apoptosis pathway by granzyme B. Proc Natl

Acad Sci U S A. 1996; 93: 11002-7.

233. Ashton-Rickardt PG. The granule pathway of programmed cell death. Crit Rev

Immunol. 2005; 25: 161-82.

234. Liu X, Zou H, Slaughter C, Wang X. DFF, a heterodimeric protein that

functions downstream of caspase-3 to trigger DNA fragmentation during

apoptosis. Cell. 1997; 89: 175-84.

235. Enari M, Sakahira H, Yokoyama H, Okawa K, Iwamatsu A, Nagata S. A

caspase-activated DNase that degrades DNA during apoptosis, and its

inhibitor ICAD. Nature. 1998; 391: 43-50.

236. Sakahira H, Enari M, Nagata S. Cleavage of CAD inhibitor in CAD activation

and DNA degradation during apoptosis. Nature. 1998; 39: 96-9.

237. Thomas DA, Du C, Xu M, Wang X, Ley TJ. DFF45/ICAD can be directly

processed by granzyme B during the induction of apoptosis. Immunity. 2000;

12: 621-32.

238. Sutton VR, Vaux DL, Trapani JA. Bcl-2 prevents apoptosis induced by perforin

and granzyme B, but not that mediated by whole cytotoxic lymphocytes. J

Immunol. 1997; 158: 5783-90.

239. Budihardjo I, Oliver H, Lutter M, Luo X, Wang X. Biochemical pathways of

caspase activation during apoptosis. Annu Rev Cell Dev Biol. 1999; 15: 269-90.

240. Thomas DA, Scorrano L, Putcha GV, Korsmeyer SJ, Ley TJ. Granzyme B can

cause mitochondrial depolarization and cell death in the absence of BID, BAX,

and BAK. Proc Natl Acad Sci U S A. 2001; 98: 14985-90.

241. Pasternack MS, Eisen HN.A novel serine esterase expressed by cytotoxic T

lymphocytes. Nature. 1985; 314: 743-5.

131

242. Shi L, Kam CM, Powers JC, Aebersold R, Greenberg AH. Purification of three

cytotoxic lymphocyte granule serine proteases that induce apoptosis through

distinct substrate and target cell interactions. J Exp Med. 1992; 176: 1521-9.

243. Beresford PJ, Xia Z, Greenberg AH, Lieberman J. Granzyme A loading induces

rapid cytolysis and a novel form of DNA damage independently of caspase

activation.Immunity. 1999; 10: 585-94.

244. Heusel JW, Wesselschmidt RL, Shresta S, Russell JH, Ley TJ. Cytotoxic

lymphocytes require granzyme B for the rapid induction of DNA

fragmentation and apoptosis in allogeneic target cells. Cell. 1994; 76: 977-87.

245. Zajac AJ, Dye JM, Quinn DG. Control of lymphocytic choriomeningitis virus

infection in granzyme B deficient mice. Virology. 2003; 305: 1-9.

246. Shresta S, Goda P, Wesselschmidt R, Ley TJ. Residual cytotoxicity and

granzyme K expression in granzyme A-deficient cytotoxic lymphocytes. J Biol

Chem. 1997; 272: 20236-44.

247. Wilharm E, Tschopp J, Jenne DE. Biological activities of granzyme K are

conserved in the mouse and account for residual Z-Lys-SBzl activity in

granzyme A-deficient mice. FEBS Lett. 1999; 459: 139-42.

248. Pereira RA, Simon MM, Simmons A. Granzyme A, a noncytolytic component

of CD8(+) cell granules, restricts the spread of herpes simplex virus in the

peripheral nervous systems of experimentally infected mice. J Virol. 2000; 74:

1029-32.

249. Shresta S, Graubert TA, Thomas DA, Raptis SZ, Ley TJ. Granzyme A initiates

an alternative pathway for granule-mediated apoptosis. Immunity. 1999; 10:

595-605.

250. Pardo J, Bosque A, Brehm R, Wallich R, Naval J, Mullbacher A, Anel A, Simon

MM. Apoptotic pathways are selectively activated by granzyme A and/or

granzyme B in CTL-mediated target cell lysis. J Cell Biol. 2004; 167: 457-68.

132

251. Martinvalet D, Zhu P, Lieberman J. Granzyme A induces caspase-independent

mitochondrial damage, a required first step for apoptosis. Immunity. 2005; 22:

355-70.

252. Fan Z, Beresford PJ, Oh DY, Zhang D, Lieberman J. Tumor suppressor NM23-

H1 is a granzyme A-activated DNase during CTL-mediated apoptosis, and the

nucleosome assembly protein SET is its inhibitor. Cell. 2003; 112: 659-72.

253. Fan Z, Beresford PJ, Zhang D, Lieberman J. HMG2 interacts with the

nucleosome assembly protein SET and is a target of the cytotoxic T-lymphocyte

protease granzyme A. Mol Cell Biol. 2002; 22: 2810-20.

254. Smyth MJ, OʹConnor MD, Trapani JA. Granzymes: a variety of serine protease

specificities encoded by genetically distinct subfamilies. J Leukoc Biol. 1996; 60:

555-62.

255. Kischkel FC, Hellbardt S, Behrmann I, Germer M, Pawlita M, Krammer PH,

Peter ME. Cytotoxicity-dependent APO-1 (Fas/CD95)-associated proteins form

a death-inducing signaling complex (DISC) with the receptor. EMBO J. 1995;

14: 5579-88.

256. Chinnaiyan AM, OʹRourke K, Tewari M, Dixit VM. FADD, a novel death

domain-containing protein, interacts with the death domain of Fas and initiates

apoptosis. Cell. 1995; 81: 505-12.

257. Boldin MP, Goncharov TM, Goltsev YV, Wallach D. Involvement of MACH, a

novel MORT1/FADD-interacting protease, in Fas/APO-1- and TNF receptor-

induced cell death. Cell. 1996; 5: 03-15.

258. Enari M, Talanian RV, Wong WW, Nagata S. Sequential activation of ICE-like

and CPP32-like proteases during Fas-mediated apoptosis. Nature. 1996; 380:

723-6.

259. Pardoll D. Does the immune system see tumors as foreign or self? Annu Rev

Immunol. 2003; 21: 807-39.

260. Smyth MJ, Godfrey DI, Trapani JA. A fresh look at tumor immunosurveillance

and immunotherapy. Nat Immunol. 2001; 2: 293-9.

133

261. Naftzger C, Houghton AN. Tumor immunology. Nat Immunol 2001; 2: 293-9.

262. Ohtani H. Stromal reaction in cancer tissue: pathophysiologic significance of

the expression of matrix-degrading enzymes in relation to matrix turnover and

immune/inflammatory reactions. Pathol Int. 1998; 48: 1-9.

263. Dano K, Romer J, Nielsen BS, Bjorn S, Pyke C, Rygaard J, Lund LR. Cancer

invasion and tissue remodeling--cooperation of protease systems and cell

types. APMIS. 1999; 107: 120-7.

264. Raulet DH. Interplay of natural killer cells and their receptors with the

adaptive immune response. Nat Immunol 2004; 5: 996-1002.

265. Raulet DH. Interplay of natural killer cells and their receptors with the

adaptive immune response. Nat Immunol 2004; 5: 996-1002.

266. Wu J, Lanier LL. Natural killer cells and cancer. Adv Cancer Res 2003; 90: 127-

56.

267. Fernandez NC, Lozier A, Flament C, Ricciardi-Castagnoli P, Bellet D, Suter

M,Perricaudet M, Tursz T, Maraskovsky E, Zitvogel L. Dendritic cells directly

trigger NK cell functions: cross-talk relevant in innate anti-tumor immune

responses in vivo. Nat Med. 1999; 5: 405-11.

268. Nishioka Y, Nishimura N, Suzuki Y, Sone S. Human monocyte-derived and

CD83(+) blood dendritic cells enhance NK cell-mediated cytotoxicity. Eur J

Immunol 2001; 31: 2633-41.

269. Borg C, Jalil A, Laderach D, Maruyama K, Wakasugi H, Charrier S, Ryffel B,

Cambi A, Figdor C, Vainchenker W, Galy A, Caignard A, Zitvogel L. NK cell

activation by dendritic cells (DCs) requires the formation of a synapse leading

to IL-12 polarization in DCs. Blood. 2004; 104: 3267-75.

270. Yu Y, Hagihara M, Ando K, Gansuvd B, Matsuzawa H, Tsuchiya T, Ueda Y,

Inoue H, Hotta T, Kato S. Enhancement of human cord blood CD34+ cell-

derived NK cell cytotoxicity by dendritic cells. J Immunol. 2001; 166: 1590-600.

134

271. Semino C, Angelini G, Poggi A, Rubartelli A. NK/iDC interaction results in IL-

18 secretion by DCs at the synaptic cleft followed by NK cell activation and

release of the DC maturation factor HMGB1. Blood 2005; 106: 609-16.

272. Granucci F, Zanoni I, Pavelka N, Van Dommelen SL, Andoniou CE, Belardelli

F,Degli Esposti MA, Ricciardi-Castagnoli P. A contribution of mouse dendritic

cell-derived IL-2 for NK cell activation. J Exp Med. 2004; 200: 287-95.

273. Osada T, Nagawa H, Kitayama J, Tsuno NH, Ishihara S, Takamizawa M,

Shibata Y. Peripheral blood dendritic cells, but not monocyte-derived dendritic

cells, can augment human NK cell function. Cell Immunol. 2001; 213: 14-23.

274. Wilson JL, Heffler LC, Charo J, Scheynius A, Bejarano MT, Ljunggren HG.

Targeting of human dendritic cells by autologous NK cells. J Immunol. 1999;

163: 6365-70.

275. Chambers BJ, Salcedo M, Ljunggren HG. Triggering of natural killer cells by

the costimulatory molecule CD80 (B7-1). Immunity. 1996; 5: 311-7.

276. Geldhof AB, Moser M, De Baetselier P. IL-12-activated NK cells recognize B7

costimulatory molecules on tumor cells and autologous dendritic cells. Adv

Exp Med Biol. 1998; 451: 203-10.

277. Turner JG, Rakhmilevich AL, Burdelya L, Neal Z, Imboden M, Sondel PM, Yu

H. Anti-CD40 antibody induces antitumor and antimetastatic effects: the role of

NK cells. J Immunol. 2001; 166: 89-94.

278. Gerosa F, Baldani-Guerra B, Nisii C, Marchesini V, Carra G, Trinchieri G.

Reciprocal activating interaction between natural killer cells and dendritic cells.

J Exp Med. 2002; 195: 327-33.

279. Vitale M, Della Chiesa M, Carlomagno S, Pende D, Arico M, Moretta L, Moretta

A. NK-dependent DC maturation is mediated by TNFalpha and IFNgamma

released upon engagement of the NKp30 triggering receptor. Blood. 2005; 106:

566-71.

135

280. Piccioli D, Sbrana S, Melandri E, Valiante NM. Contact-dependent stimulation

and inhibition of dendritic cells by natural killer cells. J Exp Med. 2002; 195:

335-41.

281. Smyth MJ, Crowe NY, Godfrey DI. NK cells and NKT cells collaborate in host

protection from methylcholanthrene-induced fibrosarcoma. Int Immunol. 2001;

13: 459-63.

282. Smyth MJ, Thia KY, Street SE, Cretney E, Trapani JA, Taniguchi M, Kawano T,

Pelikan SB, Crowe NY, Godfrey DI. Differential tumor surveillance by natural

killer (NK) and NKT cells. J Exp Med. 2000; 19: 661-8.

283. Shibolet O, Alper R, Zlotogarov L, Thalenfeld B, Engelhardt D, Rabbani E, Ilan

Y. NKT and CD8 lymphocytes mediate suppression of hepatocellular

carcinoma growth via tumor antigen-pulsed dendritic cells. Int J Cancer. 2003;

106: 236-43.

284. Kitamura H, Iwakabe K, Yahata T, Nishimura S, Ohta A, Ohmi Y, Sato M,

Takeda K,Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nishimura T. The

natural killer T (NKT) cell ligand alpha-galactosylceramide emonstrates its

immunopotentiating effect by inducing interleukin (IL)-12 production by

dendritic cells and IL-12 receptor expression on NKT cells. J Exp Med. 1999;

189: 1121-8.

285. Nishimura T, Kitamura H, Iwakabe K, Yahata T, Ohta A, Sato M, Takeda K,

Okumura K, Van Kaer L, Kawano T, Taniguchi M, Nakui M, Sekimoto M,

Koda T. The interface between innate and acquired immunity: glycolipid

antigen presentation by CD1d-expressing dendritic cells to NKT cells induces

the differentiation of antigen-specific cytotoxic T lymphocytes. Int Immunol.

2000; 12: 987-94.

286. Adam C, King S, Allgeier T, Braumuller H, Luking C, Mysliwietz J,

Kriegeskorte A, Busch DH, Rocken M, Mocikat R. DC-NK cell cross talk as a

novel CD4+ T-cell-independent pathway for antitumor CTL induction. Blood.

2005; 106: 338-44.

136

287. Hermans IF, Silk JD, Gileadi U, Salio M, Mathew B, Ritter G, Schmidt R, Harris

AL, Old L, Cerundolo V. NKT cells enhance CD4+ and CD8+ T cell responses to

soluble antigen in vivo through direct interaction with dendritic cells. J

Immunol. 2003; 171: 5140-7.

288. Verhasselt V, Buelens C, Willems F, De Groote D, Haeffner-Cavaillon N,

Goldman M. Bacterial lipopolysaccharide stimulates the production of

cytokines and the expression of costimulatory molecules by human peripheral

blood dendritic cells: evidence for a soluble CD14-dependent pathway. J

Immunol. 1997; 158: 2919-25.

289. Lu L, Qian S, Hershberger PA, Rudert WA, Lynch DH, Thomson AW. Fas

ligand (CD95L) and B7 expression on dendritic cells provide counter-

regulatory signals for T cell survival and proliferation. J Immunol. 1997; 158:

5676-84.

290. Lu L, Bonham CA, Chambers FG, Watkins SC, Hoffman RA, Simmons RL,

Thomson AW. Induction of nitric oxide synthase in mouse dendritic cells by

IFN-gamma, endotoxin, and interaction with allogeneic T cells: nitric oxide

production is associated with dendritic cell apoptosis. J Immunol. 1996; 157:

3577-86.

291. Bonham CA, Lu L, Li Y, Hoffman RA, Simmons RL, Thomson AW. Nitric oxide

production by mouse bone marrow-derived dendritic cells:implications for the

regulation of allogeneic T cell responses. Transplantation. 1996; 62: 1871-7.

292. Thurnher M, Radmayr C, Ramoner R, Ebner S, Bock G, Klocker H, Romani N,

Bartsch G. Human renal-cell carcinoma tissue contains dendritic cells. Int J

Cancer. 1996; 68: 1-7.

293. Chaux P, Favre N, Martin M, Martin F. Tumor-infiltrating dendritic cells are

defective in their antigen-presenting function and inducible B7 expression in

rats. Int J Cancer. 1997; 72: 619-24.

137

294. Zeid NA, Muller HK.S100 positive dendritic cells in human lung tumors

associated with cell differentiation and enhanced survival. Pathology. 1993; 25:

338-43.

295. Becker Y. Anticancer role of dendritic cells (DC) in human and experimental

cancers—a review. Anticancer Res. 1992; 12: 511-20.

296. Yang S, Darrow TL, Vervaert CE, Seigler HF. Immunotherapeutic potential of

tumor antigen-pulsed and unpulsed dendritic cells generated from murine

bone marrow. Cell Immunol. 1997; 179: 84-95.

297. Candido KA, Shimizu K, McLaughlin JC, Kunkel R, Fuller JA, Redman BG,

Thomas EK, Nickoloff BJ, Mule JJ. Local administration of dendritic cells

inhibits established breast tumor growth: implications for apoptosis-inducing

agents. Cancer Res. 2001; 61: 228-36.

298. Specht JM, Wang G, Do MT, Lam JS, Royal RE, Reeves ME, Rosenberg SA,

Hwu P. Dendritic cells retrovirally transduced with a model antigen gene are

therapeutically effective against established pulmonary metastases. J Exp Med.

1997; 186: 1213-21.

299. Chapoval AI, Tamada K, Chen L. In vitro growth inhibition of a broad

spectrum of tumor cell lines by activated human dendritic cells. Blood. 2000;

95: 2346-51.

300. Manna PP, Mohanakumar T. Human dendritic cell mediated cytotoxicity

against breast carcinoma cells in vitro. J Leukoc Biol. 2002; 72: 312-20.

301. Vanderheyde N, Vandenabeele P, Goldman M, Willems F. Distinct

mechanisms are involved in tumoristatic and tumoricidal activities of

monocyte-derived dendritic cells. Immunol Lett. 2004; 91: 99-101.

302. Joo HG, Fleming TP, Tanaka Y, Dunn TJ, Linehan DC, Goedegebuure PS,

Eberlein TJ. Human dendritic cells induce tumor-specific apoptosis by soluble

factors. Int J Cancer. 2002; 102: 20-8.

303. Lu G, Janjic BM, Janjic J, Whiteside TL, Storkus WJ, Vujanovic NL. Innate direct

anticancer effector function of human immature dendritic cells.II. Role of TNF,

138

lymphotoxin-alpha(1)beta(2), Fas ligand, and TNF-related apoptosis-inducing

ligand. J Immunol. 2002; 168: 1831-9.

304. Shi J, Ikeda K, Fujii N, Kondo E, Shinagawa K, Ishimaru F, Kaneda K,

Tanimoto M,Li X, Pu Q. Activated human umbilical cord blood dendritic cells

kill tumor cells without damaging normal hematological progenitor cells.

Cancer Sci. 2005; 96: 127-33.

305. Yang R, Xu D, Zhang A, Gruber A. Immature dendritic cells kill ovarian

carcinoma cells by a FAS/FASL pathway, enabling them to sensitize tumor-

specific CTLs. Int J Cancer. 2001; 94: 407-13.

306. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B,

Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18:

767-811.

307. Wykes M, Pombo A, Jenkins C, MacPherson GG. Dendritic cells interact

directly with naive B lymphocytes to transfer antigen and initiate class

switching in a primary T-dependent response. J Immunol. 1998; 161: 1313-9.

308. Dubois B, Massacrier C, Vanbervliet B, Fayette J, Briere F, Banchereau J, Caux

C. Critical role of IL-12 in dendritic cell-induced differentiation of naive B

lymphocytes. J Immunol. 1998; 161: 2223-31.

309. Wu J, Qin D, Burton GF, Szakal AK, Tew JG. Follicular dendritic cell-derived

antigen and accessory activity in initiation of memory IgG responses in vitro. J

Immunol. 1996; 157: 3404-11.

310. Dubois B, Vanbervliet B, Fayette J, Massacrier C, Van Kooten C, Briere F,

Banchereau J, Caux C. Dendritic cells enhance growth and differentiation of

CD40-activated B lymphocytes. J Exp Med. 1997; 185: 941-51.

311. MacPherson G, Kushnir N, Wykes M. Dendritic cells, B cells and the regulation

of antibody synthesis. Immunol Rev. 1999; 172: 325-34.

312. Fayette J, Dubois B, Vandenabeele S, Bridon JM, Vanbervliet B, Durand I,

Banchereau J, Caux C, Briere F. Human dendritic cells skew isotype switching

139

of CD40-activated naive B cells towards IgA1 and IgA2. J Exp Med. 1997; 185:

1909-18.

313. Wykes M, MacPherson G. Dendritic cell-B-cell interaction:dendritic cells

provide B cells with CD40-independent proliferation signals and CD40-

dependent survival signals. Immunology. 2000; 100: 1-3.

314. van Kooten C, Banchereau J. Functions of CD40 on B cells, dendritic cells and

other cells. Curr Opin Immunol. 1997; 9: 330-7.

315. Van Den Berg TK, Hasbold J, Renardel De Lavalette C, Dopp EA, Dijkstra CD,

Klaus GG. Properties of mouse CD40: differential expression of CD40 epitopes

on dendritic cells and epithelial cells. Immunology. 1996; 88: 294-300.

316. Lane P, Traunecker A, Hubele S, Inui S, Lanzavecchia A, Gray D. Activated

human T cells express a ligand for the human B cell-associated antigen CD40

which participates in T cell-dependent activation of B lymphocytes. Eur J

Immunol. 1992; 22: 2573-8.

317. Aruffo A, Farrington M, Hollenbaugh D, Li X, Milatovich A, Nonoyama S,

Bajorath J, Grosmaire LS, Stenkamp R, Neubauer M, et al. The CD40 ligand,

gp39, is defective in activated T cells from patients with X-linked hyper-IgM

syndrome. Cell. 1993; 72: 291-300.

318. Conley ME, Larche M, Bonagura VR, Lawton AR 3rd, Buckley RH, Fu SM,

Coustan-Smith E, Herrod HG, Campana D. Hyper IgM syndrome associated

with defective CD40-mediated B cell activation. J Clin Invest. 1994; 94: 1404-9.

319. Levy J, Espanol-Boren T, Thomas C, Fischer A, Tovo P, Bordigoni P, Resnick

I,Fasth A, Baer M, Gomez L, Sanders EA, et al. Clinical spectrum of X-linked

hyper-IgM syndrome. J Pediatr. 1997; 131: 47-54.

320. DiSanto JP, Bonnefoy JY, Gauchat JF, Fischer A, de Saint Basile G. CD40 ligand

mutations in x-linked immunodeficiency with hyper-IgM. Nature. 1993; 361:

541-3.

321. Locksley RM, Killeen N, Lenardo MJ. The TNF and TNF receptor

superfamilies: integrating mammalian biology. Cell. 2001; 104: 487-501.

140

322. Cheng G, Cleary AM, Ye ZS, Hong DI, Lederman S, Baltimore D. Involvement

of CRAF1, a relative of TRAF, in CD40 signaling. Science. 1995; 267: 1494-8.

323. Rothe M, Sarma V, Dixit VM, Goeddel DV. TRAF2-mediated activation of NF-

kappa B by TNF receptor 2 and CD40. Science. 1995; 269: 1424-7.

324. Ishida TK, Tojo T, Aoki T, Kobayashi N, Ohishi T, Watanabe T, Yamamoto T,

Inoue J. TRAF5, a novel tumor necrosis factor receptor-associated factor family

protein, mediates CD40 signaling. Proc Natl Acad Sci U S A. 1996; 93: 9437-42.

325. Pullen SS, Dang TT, Crute JJ, Kehry MR. CD40 signaling through tumor

necrosis factor receptor-associated factors (TRAFs). Binding site specificity and

activation of downstream pathways by distinct TRAFs. J Biol Chem. 1999; 274:

14246-54.

326. Tsukamoto N, Kobayashi N, Azuma S, Yamamoto T, Inoue J. Two differently

regulated nuclear factor kappaB activation pathways triggered by the

cytoplasmic tail of CD40. Proc Natl Acad Sci U S A. 1999; 96: 1234-9.

327. Leo E, Welsh K, Matsuzawa S, Zapata JM, Kitada S, Mitchell RS, Ely KR, Reed

JC. Differential requirements for tumor necrosis factor receptor-associated

factor family proteins in CD40-mediated induction of NF-kappaB and Jun N-

terminal kinase activation. J Biol Chem. 1999; 274: 22414-22.

328. Aicher A, Shu GL, Magaletti D, Mulvania T, Pezzutto A, Craxton A, Clark EA.

Differential role for p38 mitogen-activated protein kinase in regulating CD40-

induced gene expression in dendritic cells and B cells. J Immunol. 1999; 163:

5786-95.

329. Hanissian SH, Geha RS. Jak3 is associated with CD40 and is critical for CD40

induction of gene expression in B cells. Immunity. 1997; 6: 379-87.

330. Karras JG, Wang Z, Huo L, Frank DA, Rothstein TL. Induction of STAT protein

signaling through the CD40 receptor in B lymphocytes:distinct STAT activation

following surface Ig and CD40 receptor engagement. J Immunol. 1997; 159:

4350-5.

141

331. Ouaaz F, Arron J, Zheng Y, Choi Y, Beg AA. Dendritic cell development and

survival require distinct NF-kappaB subunits. Immunity. 2002; 16: 257-70.

332. Wu L, DʹAmico A, Winkel KD, Suter M, Lo D, Shortman K. RelB is essential for

the development of myeloid-related CD8alpha- dendritic cells but not of

lymphoid-related CD8alpha+ dendritic cells. Immunity. 1998; 9: 839-47.

333. Fazekas De St Groth B, L Smith A, Bosco J, Sze DM, Power CA, Austen FI.

Experimental models linking dendritic cell lineage, phenotype and function.

Immunol Cell Biol. 2002; 80: 469-76.

334. Burkly L, Hession C, Ogata L, Reilly C, Marconi LA, Olson D, Tizard R, Cate

R,Lo D. Expression of relB is required for the development of thymic medulla

and dendritic cells. Nature. 1995; 373: 531-6.

335. DiMolfetto L, Reilly C, Wei Q, Lo D. Dendritic-like cells from relB mutant mice.

Adv Exp Med Biol. 1997; 417: 47-54.

336. Weih F, Warr G, Yang H, Bravo R. Multifocal defects in immune responses in

RelB-deficient mice. J Immunol. 1997; 158: 5211-8.

337. Martin E, OʹSullivan B, Low P, Thomas R. Antigen-specific suppression of a

primed immune response by dendritic cells mediated by regulatory T cells

secreting interleukin-10. Immunity. 2003; 18: 155-67.

338. Ardeshna KM, Pizzey AR, Devereux S, Khwaja A. The PI3 kinase, p38 SAP

kinase, and NF-kappaB signal transduction pathways are involved in the

survival and maturation of lipopolysaccharide-stimulated human monocyte-

derived dendritic cells. Blood. 2000; 96: 1039-46.

339. Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C.A critical role for p38

mitogen-activated protein kinase in the maturation of human blood-derived

dendritic cells induced by lipopolysaccharide, TNF-α, and contact sensitizers. J

Immunol. 2001; 166: 3837-45.

340. Saccani S, Pantano S, Natoli G. p38-Dependent marking of inflammatory genes

for increased NF-kappa B recruitment. Nat Immunol. 2002; 3: 69-75.

142

341. Yewdell JW, Norbury CC, Bennink JR. Mechanisms of exogenous antigen

presentation by MHC class I molecules in vitro and in vivo: implications for

generating CD8+ T cell responses to infectious agents, tumors, transplants, and

vaccines. Adv Immunol. 1999; 73: 1-77.

342. Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, Pulendran B,

Palucka K. Immunobiology of dendritic cells. Annu Rev Immunol. 2000; 18:

767-811.

343. Hartmann G, Weiner GJ, Krieg AM. CpG DNA: a potent signal for growth,

activation, and maturation of human dendritic cells. Proc Natl Acad Sci U S A.

1999; 96: 9305-10.

344. Rescigno M, Granucci F, Citterio S, Foti M, Ricciardi-Castagnoli P. Coordinated

events during bacteria-induced DC maturation. Immunol Today. 1999; 20: 200-

3.

345. Cella M, Scheidegger D, Palmer-Lehmann K, Lane P, Lanzavecchia A, Alber G.

Ligation of CD40 on dendritic cells triggers production of high levels of

interleukin-12 and enhances T cell stimulatory capacity: T-T help via APC

activation. J Exp Med. 1996; 184: 747-52.

346. Koch F, Stanzl U, Jennewein P, Janke K, Heufler C, Kampgen E, Romani N,

Schuler G. High level IL-12 production by murine dendritic cells: upregulation

via MHC class II and CD40 molecules and downregulation by IL-4 and IL-10. J

Exp Med. 1996; 184: 741-6.

347. Kelsall BL, Stuber E, Neurath M, Strober W. Interleukin-12 production by

dendritic cells. The role of CD40-CD40L interactions in Th1 T-cell responses.

Ann N Y Acad Sci. 1996; 795: 116-26.

348. Watford WT, Moriguchi M, Morinobu A, OʹShea JJ. The biology of IL-12:

coordinating innate and adaptive immune responses. Cytokine Growth Factor

Rev. 2003; 14: 361-8.

349. Ohteki T. Critical role for IL-15 in innate immunity. Curr Mol Med. 2002; 2:

371-80.

143

350. Tan JT, Ernst B, Kieper WC, LeRoy E, Sprent J, Surh CD. Interleukin (IL)-15 and

IL-7 jointly regulate homeostatic proliferation of memory phenotype CD8+

cells but are not required for memory phenotype CD4+ cells. J Exp Med. 2002;

195: 1523-32.

351. Schluns KS, Williams K, Ma A, Zheng XX, Lefrancois L. Cutting edge:

requirement for IL-15 in the generation of primary and memory antigen-

specific CD8 T cells. J Immunol. 2002; 168: 4827-31.

352. Yajima T, Nishimura H, Ishimitsu R, Watase T, Busch DH, Pamer EG, Kuwano

H,Yoshikai Y. Overexpression of IL-15 in vivo increases antigen-driven

memory CD8+ T cells following a microbe exposure. J Immunol. 2002; 168:

1198-203.

353. Kieper WC, Tan JT, Bondi-Boyd B, Gapin L, Sprent J, Ceredig R, Surh CD.

Overexpression of interleukin (IL)-7 leads to IL-15-independent generation of

memory phenotype CD8+ T cells. J Exp Med. 2002; 195: 1533-9.

354. Becker TC, Wherry EJ, Boone D, Murali-Krishna K, Antia R, Ma A, Ahmed R.

Interleukin 15 is required for proliferative renewal of virus-specific memory

CD8 T cells. J Exp Med. 2002; 195: 1541-8.

355. van Kooten C, Banchereau J. CD40-CD40 ligand. J Leukoc Biol. 2000; 67: 2-17.

356. Alderson MR, Armitage RJ, Tough TW, Strockbine L, Fanslow WC, Spriggs

MK. CD40 expression by human monocytes: regulation by cytokines and

activation of monocytes by the ligand for CD40. J Exp Med. 1993; 178: 669-74.

357. Bleharski JR, Niazi KR, Sieling PA, Cheng G, Modlin RL. Signaling

lymphocytic activation molecule is expressed on CD40 ligand-activated

dendritic cells and directly augments production of inflammatory cytokines. J

Immunol. 2001; 167: 3174-81.

358. Sozzani S, Allavena P, DʹAmico G, Luini W, Bianchi G, Kataura M, Imai T,

Yoshie O, Bonecchi R, Mantovani A. Differential regulation of chemokine

receptors during dendritic cell maturation: a model for their trafficking

properties. J Immunol. 1998; 161: 1083-6.

144

359. Sallusto F, Schaerli P, Loetscher P, Schaniel C, Lenig D, Mackay CR, Qin

S,Lanzavecchia A. Rapid and coordinated switch in chemokine receptor

expression during dendritic cell maturation. Eur J Immunol. 1998; 28: 2760-9.

360. Gunn MD, Tangemann K, Tam C, Cyster JG, Rosen SD, Williams LT. A

chemokine expressed in lymphoid high endothelial venules promotes the

adhesion and chemotaxis of naive T lymphocytes. Proc Natl Acad Sci U S A.

1998; 95: 258-63.

361. Bennett SR, Carbone FR, Karamalis F, Flavell RA, Miller JF, Heath WR. Help

for cytotoxic-T-cell responses is mediated by CD40 signalling. Nature. 1998;

393: 478-80.

362. Labeur MS, Roters B, Pers B, Mehling A, Luger TA, Schwarz T, Grabbe S.

Generation of tumor immunity by bone marrow-derived dendritic cells

correlates with dendritic cell maturation stage. J Immunol. 1999; 162: 168-75.

363. OʹSullivan BJ, Thomas R. CD40 ligation conditions dendritic cell antigen-

presenting function through sustained activation of NF-kappaB. J Immunol.

2002; 168: 5491-8.

364. Ardeshna KM, Pizzey AR, Devereux S, Khwaja A. The PI3 kinase, p38 SAP

kinase, and NF-kappaB signal transduction pathways are involved in the

survival and maturation of lipopolysaccharide-stimulated human monocyte-

derived dendritic cells. Blood. 2000; 6: 039-46.

365. Arrighi JF, Rebsamen M, Rousset F, Kindler V, Hauser C. A critical role for p38

mitogen-activated protein kinase in the maturation of human blood-derived

dendritic cells induced by lipopolysaccharide, TNF-alpha, and contact

sensitizers. J Immunol. 2001; 166: 3837-45.

366. Valenzuela J, Schmidt C, Mescher M. The roles of IL-12 in providing a third

signal for clonal expansion of naive CD8 T cells. J Immunol. 2002; 169: 6842-9.

367. OʹSullivan BJ, MacDonald KP, Pettit AR, Thomas R. RelB nuclear translocation

regulates B cell MHC molecule, CD40 expression, and antigen-presenting cell

function. Proc Natl Acad Sci U S A. 2000; 97: 11421-6.

145

368. Dejardin E, Deregowski V, Greimers R, Cai Z, Chouaib S, Merville MP, Bours

V. Regulation of major histocompatibility complex class I expression by NF-

kappaB-related proteins in breast cancer cells. Oncogene. 1998; 16: 3299-307.

369. Peng X, Remacle JE, Kasran A, Huylebroeck D, Ceuppens JL. IL-12 up-

regulates CD40 ligand (CD154) expression on human T cells. J Immunol. 1998;

160: 1166-72.

370. Prilliman KR, Lemmens EE, Palioungas G, Wolfe TG, Allison JP, Sharpe AH,

Schoenberger SP. Cutting edge: a crucial role for B7-CD28 in transmitting T

help from APC to CTL. J Immunol. 2002; 169: 4094-7.

371. Bluestone JA, Abbas AK. Natural versus adaptive regulatory T cells. Nat Rev

Immunol. 2003; 3: 253-7.

372. Hawiger D, Inaba K, Dorsett Y, Guo M, Mahnke K, Rivera M, Ravetch JV,

Steinman RM, Nussenzweig MC. Dendritic cells induce peripheral T cell

unresponsiveness under steady state conditions in vivo. J Exp Med. 2001; 194:

769-79.

373. Munn DH. Indoleamine 2,3-dioxygenase, tumor-induced tolerance and

counter-regulation. Curr Opin Immunol. 2006; 18: 220-5.

374. Steinman RM, Turley S, Mellman I, Inaba K. The induction of tolerance by

dendritic cells that have captured apoptotic cells. J Exp Med. 2000; 191: 411-6.

375. Wilson NS, El-Sukkari D, Belz GT, Smith CM, Steptoe RJ, Heath WR, Shortman

K, Villadangos JA. Most lymphoid organ dendritic cell types are

phenotypically and functionally immature. Blood. 2003; 102: 2187-94.

376. Bonifaz L, Bonnyay D, Mahnke K, Rivera M, Nussenzweig MC, Steinman RM.

Efficient targeting of protein antigen to the dendritic cell receptor DEC-205 in

the steady state leads to antigen presentation on major histocompatibility

complex class I products and peripheral CD8+ T cell tolerance. J Exp Med. 2002;

196: 1627-38.

146

377. Groux H, OʹGarra A, Bigler M, Rouleau M, Antonenko S, de Vries JE,

Roncarolo MG. A CD4+ T-cell subset inhibits antigen-specific T-cell responses

and prevents colitis. Nature. 1997; 389: 737-42.

378. Martin E, OʹSullivan B, Low P, Thomas R. Antigen-specific suppression of a

primed immune response by dendritic cells mediated by regulatory T cells

secreting interleukin-10. Immunity. 2003; 18: 155-67.

379. Roth E, Schwartzkopff J, Pircher H. CD40 ligation in the presence of self-

reactive CD8 T cells leads to severe immunopathology. J Immunol. 2002; 168:

5124-9.

380. Diehl L, den Boer AT, Schoenberger SP, van der Voort EI, Schumacher TN,

Melief CJ, Offringa R, Toes RE. CD40 activation in vivo overcomes peptide-

induced peripheral cytotoxic T-lymphocyte tolerance and augments anti-tumor

vaccine efficacy. Nat Med. 1999; 5: 774-9.

381. Pellat-Deceunynck C, Amiot M, Robillard N, Wijdenes J, Bataille R. CD11a-

CD18 and CD102 interactions mediate human myeloma cell growth arrest

induced by CD40 stimulation. Cancer Res. 1996; 56: 1909-16.

382. Funakoshi S, Longo DL, Beckwith M, Conley DK, Tsarfaty G, Tsarfaty I,

Armitage RJ, Fanslow WC, Spriggs MK, Murphy WJ. Inhibition of human B-

cell lymphoma growth by CD40 stimulation. Blood. 1994; 83: 2787-94.

383. Planken EV, Dijkstra NH, Willemze R, Kluin-Nelemans JC. Proliferation of B

cell malignancies in all stages of differentiation upon stimulation in the ʹCD40

systemʹ. Leukemia. 1996; 10: 488-93.

384. Challa A, Eliopoulos AG, Holder MJ, Burguete AS, Pound JD, Chamba A,

Grafton G, Armitage RJ, Gregory CD, Martinez-Valdez H, Young L, Gordon J.

Population depletion activates autonomous CD154-dependent survival in

biopsylike Burkitt lymphoma cells. Blood. 2002; 99: 3411-8.

385. Lee HH, Dadgostar H, Cheng Q, Shu J, Cheng G. NF-kappaB-mediated up-

regulation of Bcl-x and Bfl-1/A1 is required for CD40 survival signaling in B

lymphocytes. Proc Natl Acad Sci U S A. 1999; 96: 9136-41.

147

386. Mackey MF, Gunn JR, Ting PP, Kikutani H, Dranoff G, Noelle RJ, Barth RJ Jr.

Protective immunity induced by tumor vaccines requires interaction between

CD40 and its ligand, CD154. Cancer Res. 1997; 57: 2569-74.

387. van Mierlo GJ, den Boer AT, Medema JP, van der Voort EI, Fransen MF,

Offringa R, Melief CJ, Toes RE. CD40 stimulation leads to effective therapy of

CD40(-) tumors through induction of strong systemic cytotoxic T lymphocyte

immunity. Proc Natl Acad Sci U S A. 2002; 99: 5561-6.

388. Tutt AL, OʹBrien L, Hussain A, Crowther GR, French RR, Glennie MJ. T cell

immunity to lymphoma following treatment with anti-CD40 monoclonal

antibody. J Immunol. 2002; 168: 2720-8.

389. Kedl RM, Jordan M, Potter T, Kappler J, Marrack P, Dow S. CD40 stimulation

accelerates deletion of tumor-specific CD8(+) T cells in the absence of tumor-

antigen vaccination. Proc Natl Acad Sci U S A. 2001; 98: 10811-6.

390. Ochsenbein AF. Immunological ignorance of solid tumors. Springer Semin

Immunopathol. 2005; 27: 19-35.

391. Oppenheim DE, Roberts SJ, Clarke SL, Filler R, Lewis JM, Tigelaar RE, Girardi

M, Hayday AC. Sustained localized expression of ligand for the activating

NKG2D receptor impairs natural cytotoxicity in vivo and reduces tumor

immunosurveillance. Nat Immunol. 2005; 6: 928-37.

392. Wiemann K, Mittrucker HW, Feger U, Welte SA, Yokoyama WM, Spies T,

Rammensee HG,Steinle A. Systemic NKG2D down-regulation impairs NK and

CD8 T cell responses in vivo. J Immunol. 2005; 175: 720-9.

393. Cabrera T, Lopez-Nevot MA, Gaforio JJ, Ruiz-Cabello F, Garrido F. Analysis of

HLA expression in human tumor tissues. Cancer Immunol Immunother. 2003;

52: 1-9.

394. Campoli M, Chang CC, Ferrone S. HLA class I antigen loss, tumor immune

escape and immune selection. Vaccine. 2002; 20: 40-5.

148

395. Ciocca DR, Calderwood SK. Heat shock proteins in cancer: diagnostic,

prognostic, predictive, and treatment implications. Cell Stress Chaperones.

2005; 10: 86-103.

396. Melcher A, Todryk S, Hardwick N, Ford M, Jacobson M, Vile RG. Tumor

immunogenicity is determined by the mechanism of cell death via induction of

heat shock protein expression. Nat Med. 1998; 4: 581-7.

397. Multhoff G. Activation of natural killer cells by heat shock protein 70. Int J

Hyperthermia. 2002; 18: 576-85.

398. Beckman RA, Loeb LA. Genetic instability in cancer: theory and experiment.

Semin Cancer Biol. 2005; 15: 423-35.

399. Chen Q, Daniel V, Maher DW, Hersey P. Production of IL-10 by melanoma

cells: examination of its role in immunosuppression mediated by melanoma.

Int J Cancer. 1994 ; 56: 755-60.

400. Tada T, Ohzeki S, Utsumi K, Takiuchi H, Muramatsu M, Li XF, Shimizu J,

Fujiwara H, Hamaoka T. Transforming growth factor-beta-induced inhibition

of T cell function. Susceptibility difference in T cells of various phenotypes and

functions and its relevance to immunosuppression in the tumor-bearing state. J

Immunol. 1991; 146: 1077-82.

401. Inge TH, Hoover SK, Susskind BM, Barrett SK, Bear HD.Inhibition of tumor-

specific cytotoxic T-lymphocyte responses by transforming growth factor beta

1.Cancer Res. 1992; 52: 1386-92.

402. Strand S, Hofmann WJ, Hug H, Muller M, Otto G, Strand D, Mariani SM,

Stremmel W, Krammer PH, Galle PR. Lymphocyte apoptosis induced by CD95

(APO-1/Fas) ligand-expressing tumor cells--a mechanism of immune evasion?

Nat Med. 1996; 2: 1361-6.

403. Shurin GV, Gerein V, Lotze MT, Barksdale EM Jr. Apoptosis induced in T cells

by human neuroblastoma cells: role of Fas ligand. Nat Immun 1998; 16: 263-74.

404. Gastman BR, Atarshi Y, Reichert TE, Saito T, Balkir L, Rabinowich H,

Whiteside TL. Fas ligand is expressed on human squamous cell carcinomas of

149

the head and neck, and it promotes apoptosis of T lymphocytes. Cancer Res.

1999; 59: 5356-64.

405. Dong H, Strome SE, Salomao DR, Tamura H, Hirano F, Flies DB, Roche PC, Lu

J, Zhu G, Tamada K, Lennon VA, Celis E, Chen L. Tumor-associated B7-H1

promotes T-cell apoptosis: a potential mechanism of immune evasion. Nat

Med. 2002;8:93-800.

406. Muta K, Ohshima K, Abe Y, Uike N, Choi I, Matsushima T, Nishimura J,

Kikuchi M,Nakashima M, Watanabe T, Nawata H. Expression of human

tumor-associated antigen RCAS1 in adult T-cell leukemia/lymphoma. Int J

Hematol. 2004; 79: 340-4.

407. Uyttenhove C, Pilotte L, Theate I, Stroobant V, Colau D, Parmentier N, Boon

T,Van den Eynde BJ. Evidence for a tumoral immune resistance mechanism

based on tryptophan degradation by indoleamine 2,3-dioxygenase. Nat Med.

2003; 9: 1269-74.

408. Fallarino F, Grohmann U, Vacca C, Bianchi R, Orabona C, Spreca A, Fioretti

MC,Puccetti P. T cell apoptosis by tryptophan catabolism. Cell Death Differ.

2002; 9: 1069-77.

409. Curiel TJ, Coukos G, Zou L, Alvarez X, Cheng P, Mottram P, Evdemon-Hogan

M, Conejo-Garcia JR, Zhang L, Burow M et al. Specific recruitment of

regulatory T cells in ovarian carcinoma fosters immune privilege and predicts

reduced survival. Nat Med. 2004 10: 942-9.

410. Antony PA, Piccirillo CA, Akpinarli A, Finkelstein SE, Speiss PJ, Surman

DR,Palmer DC, Chan CC, Klebanoff CA et al. CD8+ T cell immunity against a

tumor/self-antigen is augmented by CD4+ T helper cells and hindered by

naturally occurring T regulatory cells. J Immunol. 2005; 174: 2591-601.

411. Riethmuller G, Schneider-Gadicke E, Johnson JP. Monoclonal antibodies in

cancer therapy. Curr Opin Immunol.1993; 5: 732-9.

412. Weiner LM, Adams GP. New approaches to antibody therapy. Oncogene. 2000;

19: 6144-51.

150

413. Urban JL, Schreiber H. Tumor antigens. Annu Rev Immunol.1992; 10: 617-44.

414. Boon T, Cerottini JC, Van den Eynde B, van der Bruggen P, Van Pel A. Tumor

antigens recognized by T lymphocytes. Annu Rev Immunol. 1994; 12: 337-65.

415. Adema GJ, Hartgers F, Verstraten R, de Vries E, Marland G, Menon S, Foster J,

Xu Y, Nooyen P, McClanahan T, Bacon KB, Figdor CG. A dendritic-cell-

derived C-C chemokine that preferentially attracts naive T cells. Nature. 1997;

387: 713-7.

416. Mayordomo JI, Loftus DJ, Sakamoto H, De Cesare CM, Appasamy PM, Lotze

MT, Storkus WJ, Appella E, DeLeo AB. Therapy of murine tumors with p53

wild-type and mutant sequence peptide-based vaccines. J Exp Med. 1996; 183:

1357-65.

417. Holtl L, Zelle-Rieser C, Gander H, Papesh C, Ramoner R, Bartsch G, Rogatsch

H, Barsoum AL, Coggin JH Jr, Thurnher M. Immunotherapy of metastatic renal

cell carcinoma with tumor lysate-pulsed autologous dendritic cells. Clin Cancer

Res. 2002; 8: 3369-76.

418. Boczkowski D, Nair SK, Snyder D, Gilboa E. Dendritic cells pulsed with RNA

are potent antigen-presenting cells in vitro and in vivo. J Exp Med.1996; 184:

465-72.

419. Jenne L, Schuler G, Steinkasserer A. Viral vectors for dendritic cell-based

immunotherapy. Trends Immunol. 2001; 22: 102-107.

420. Leach DR, Krummel MF, Allison JP. Enhancement of antitumor immunity by

CTLA-4 blockade. Science. 1996; 271: 1734-6.

421. Von Boehmer