S. Donina1,2, S. Chapenko1, I. Jaunalksne1,3,

M. Chistjakovs1, M. Murovska1

1 Riga Stradin's University,

A.Kirchenstein's Institute of Microbiology and Virusology 2 Riga East University Hospital 3 Riga Stradin's Clinical University Hospital

Riga, LATVIA – October 13-14, 2011

“Promotion of International Cooperation Activities of Riga Stradiņš

University in Science and Technologies”, agreement

No. 2010/0200/2DP/2.1.1.2.0/10/APIA/VIAA/006

Human Herpes Viruses 6 and 7

(HHV6 and HHV7)

Present in patients with compromised immune system

Are immunotropic and immunomodulating

Can induce Fas-mediated apoptosis in lymphocytes

CD4+

CD8+

Mo/Mf

NK

Target cells

● Tumor immunosuppressive factors

(TGF-beta, LBIF)

● Chronic stimulation of T-cells by tumor

● Disorder of APC activity

Cancer Patients Immune System

Is Influenced By

Insufficiency of cellular response

Contribution of tumor escape

Aim of the Study

to clarify the influence of HHV6 and HHV7

on cellular immunity

in gastrointestinal (GI) cancer patients

before any treatment

Material and Methods

GI cancer, Stage I–III 95 patients:

● Colorectal cancer (CRC) 63

● Gastric cancer 32

Age range: 38–75 years

Gender:

● Male 45

● Female 50

Lymphocyte subsets CD3+, CD4+, CD8+, CD16+, CD19+,

CD38+, CD25+, CD95+ were detected by laser-flow cytometer

(Becton Dickenson)

Viral sequences in DNA from PBL and plasma were detected

by nPCR

latent 61 (64%)

negative 34 (36%)

latent 62 (65%)

negative 33 (35%)

active 22

active 23

negative 81 (85%)

latent 14 (15%)

active 1

HHV6 and HHV7 in GI Cancer Patients

latent 12 (13%)

negative 83 (87%)

HHV6 and/or HHV7

HHV7 HHV6

HHV6 + HHV7

0

500

1000

1500

2000

2500

Group I 1545 854 665 609 407 175 1086 170 1,3

Group II 802 443 369 318 209 117 556 95 1,2

CD3+ CD4+ CD8+ CD38+ CD16+ CD19+ CD95+ CD25+CD4/

/CD8

Group I (n=54): Lymphocytes ≥1400 Group II (n=41): Lymphocytes <1400

*p<0.05

*

*

* * * *

*

cells

per

1 m

m2

Average Count of Immuncompetent Cells

in GI Cancer Patients in Group I and II

CD3 CD4 CD8 CD38 CD16 CD19 CD95 CD25 CD4/

/CD8

Group I 1545 ±523

854 ±299

665 ±386

609 ±248

407 ±266

175 ±19

1086 ±394

170 ±146

1,3 ±0,4

Group II 802 ±209

443 ±169

369 ±151

318 ±105

209 ±129

117 ±115

556 ±165

95 ±49

1,2 ±0,3

0

500

1000

1500

2000

2500

negative 1489 857 616 164 430 618 1065 150

latent 1461 795 634 156 388 592 1013 188

active 1789 976 789 241 421 638 1267 152

CD3+ CD4+ CD8+ CD19+ CD16+ CD38+ CD95+ CD25+

cells

per

1 m

m2

Average Count of Immuncompetent Cells

in GI Cancer Patients Group I

According to HHV6/HHV7 Infection

HHV6+HHV7

infection CD3 CD4 CD8 CD19 CD16 CD38 CD95 CD25

negative 1489 ±660

857 ±407

616 ±408

164 ±83

430 ±287

618 ±252

1065 ±436

150 ±93

latent 1461 ±335

795 ±234

634 ±188

156 ±80

388 ±272

592 ±272

1013 ±259

188 ±186

active 1789 ±635

976 ±259

789 ±619

241 ±188

421 ±240

638 ±193

1267 ±535

152 ±82

0

200

400

600

800

1000

1200

negative 781 446 358 120 238 337 521 101

latent 890 479 404 118 159 285 644 76

active 758 400 356 107 197 312 543 103

CD3+ CD4+ CD8+ CD19+ CD16+ CD38+ CD95+ CD25+

cells

per

1 m

m2

Average Count of Immuncompetent Cells

in GI Cancer Patients Group II

According to HHV6/HHV7 Infection

HHV6+HHV7

infection CD3 CD4 CD8 CD19 CD16 CD38 CD95 CD25

negative 781 ±200

446 ±199

358 ±142

120 ±52

238 ±40

337 ±136

521 ±169

101 ±58

latent 890 ±166

479 ±76

404 ±147

118 ±52

159 ±31

285 ±54

644 ±145

76 ±29

active 758 ±264

400 ±164

356 ±189

107 ±71

197 ±35

312 ±58

543 ±165

103 ±38

Number of CD4+ and CD25+ Cells

in Immunocompetent (Group I) and

Immunocompromised (Group II) GI Cancer Patients

According to HHV6/HHV7 Infection

400

976

479

795

446

857

103152

76

188

101150

0

100

200

300

400

500

600

700

800

900

1000

Group I Group II Group I Group II Group I Group II

negative latent active

CD4+ CD4+

CD4+ CD4+

CD4+

CD4+

CD25+ CD25+

CD25+

CD25+ CD25+

CD25+

CD4+/CD8+ in Immunocompetent (Group I) and

Immunocompromised (Group II) GI Cancer Patients

According to HHV6/HHV7 Infection

1,2 1,21,1

1,41,3

1,2

0,0

0,2

0,4

0,6

0,8

1,0

1,2

1,4

1,6

1,8

2,0

Group I Group II Group I Group II Group I Group II

negative latent active

Example:

1270

1,4

178

809

148

368

900

12391132

1,0

213

884

112

742

446442

0

300

600

900

1200

1500

CD4+ CD8+ CD16+ CD19+ CD38+ CD25+ CD95+ CD4/CD8

A B

A B A A A A A A B B B B B B

Absolute Count of Lymphocytes

Among Immunocompetent

GI Cancer Patients A and B

Conclusions

56,8% of GI cancer patients in our study are associated with a

compromised immune system (lymphopenia, Grade I–III)

65% of examined GI ca patients had latent HHV6 or/and HHV7

infection and 37% of them had active viral infection

Insufficiency of inductor–phase of cellular immune response

as well as non–specific effector–phase was typical in patients

with lymphopenia and active beta–herpes virus infection

Average number of lymphocyte subsets in patient groups did not

reflect individual immune response and intensity of cellular immune

reactions in each patient

“Promotion of International Cooperation Activities of Riga Stradiņš

University in Science and Technologies”, agreement

No. 2010/0200/2DP/2.1.1.2.0/10/APIA/VIAA/006