a b cd45+ - nature · rsad2 radical s-adenosyl methionine domain containing 2 58185 3.36...

c

0

1

2

3

4 Rsad2

Fo

ld c

ha

ng

e

0

0.5

1

1.5

2

2.5 Irf7 Mx1

0

1

2

3

4 Dhx58

Fo

ld c

ha

ng

e

Ifit2

Trim30a Ifi205 Ifnb1

aCD45−

Fo

ld c

ha

ng

e

b

0

2

4

6

8

10

Trim

30a

Ifnb1

Dhx

58Ccl4

Rsa

d2

Mav

s

Cxc

l10

Il15

Il12a

Cxc

l1M

x1 Ifi2

Tlr3Ccl7

TnfCcl3

Mx2 Irf

7

Ifit2

05Ccl2

Irf1

Oas

2

***

**

*

Fo

ld c

ha

ng

e

Irf3

* ** *

* *

NS

NS

NS

NS

*

NS

*

NS

NS

*NS

*

**

NS*

NS

*

**

NS*

*

NS

*

*

NS

*

*NS

* *

NS

**

NS

**

NS

**

NS

*

*

NS

*

*NS

*NS

*

NS

NS

*

*

NS

*

NS

NS

*

NS

*

CD45+

0

2

4

8

12

Trim

30a

Ifnb1

Dhx

58

Cxc

l10

Rsa

d2

Mav

sM

x1Ccl4

Il12a

Cxc

l1Ifi2

Il15

Tlr3Ccl7

Mx2

Ccl3

Tnf Irf7

Ifit2

05Ccl2

Irf1

Oas

2

Day 4Day 2

Day 8

Irf3

*

NSNS

NS

NS

NS

NSNS

NS

NSNS

NSNS

* NS

NS

*

NS

*

NS

*

NS

NS

NS

*****

*

*

**

**

NS

*

NS

*NS

NS

NSNS

NS

NS

NSNS

NS

****

***

***

***

NS

NS NSNS

NS

NS

NSNS

NSNS

NSNS

NS NSNS

NS

NS NS NS

NS

NS

NS

NS

d

5

10

20

Fo

ld c

ha

ng

e 15

0

WT_6

Il15M

x1 Irf2

Ccl7Ccl3

Rsa

d2

Cxc

l10

Ifnb1

Ifi20

5Irf

3

**

***

***

** **

**

0

DXPBS

WT_10

2

4

12

8

Rsa

d2

Cxc

l10

Irf2

Ccl3M

x1

Ifnb1Il1

5Ccl7

Irf3

Ifi20

5

**

***

**

0

5

10

15

20

25

Fo

ld c

ha

ng

e

e

OXPPBS

ex vivo

*

in vitro

**

Supplementary Figure 1

Ly6G

+

Ly6C

high

Ly6C

low

Ly6G

+

Ly6C

high

Ly6C

low

Ly6G

+

Ly6C

high

Ly6C

low

Ly6G

+

Ly6C

high

Ly6C

low

Ifnb1

DXPBS

Day 4Day 2

Day 8

0

0.5

1

1.5

2

2.5

0

0.5

1

1.5

2

2.5

0

0.5

1

1.5

2

2.5

0

1

2

3

4

0

0.5

1

1.5

2

2.5

Nature Medicine: doi:10.1038/nm.3708

b

0

100

200

300

400

0 5 10 15 20

Tu

mo

r siz

e (m

m2

)

WT MCA205 Ifnar1−/−_7 MCA205 a

PBS

DX

**

NS

Time (d)

0 5 10 15 20

Time (d)

0

100

200

300

400

0

2

4

6

8

Cxcl1

0 (n

g m

l )

*

*** PBSDXrIfn-α

WT Ifnar1−/−_7

15.9

±0,5

NSNS


c

0

5

10

15

20

25 PBSrIfn-αrIfn-γ

***

***

NS

Ifnar1−/−_7

***

MH

C-I

exp

ressio

n (

MF

I)

WT

MCA205 MCA205

−1


a

DAPI− AnnV+

Mo

rtalit

y (

%)

100

80

60

0

40

20

DAPI+P

BS

DX

MT

XC

DD

P

Mito

C

MCA205 WT_6 Ifih1−/−_1985 Ifih1−/−_1989

PB

SD

XM

TX

CD

DP

Mito

C

Tlr3−/−_3 Tlr3−/−_4 Ticam1−/−_1 Ticam1−/−_2b

Fo

ld c

ha

ng

e

c

Fo

ld c

ha

ng

e

Ifna4

PBS

Ifnb1 Irf7WT_6

Ifih1−/−_1985

Ifih1−/−_1989

Tlr3−/−_3

Tlr3−/−_4

Ticam1−/−_1

Ticam1−/−_2

DX

Ifna2

PBS DX PBS DX PBS DXd

Fo

ld c

ha

ng

e

0

50

100

150

200

300

600

900Ifna4 Ifnb1

PBS

DX

MTX

CDDP

Mito

C0

PBS

DX

MTX

CDDP

Mito

C0

200

250

300

350

PBS

DX

MTX

CDDP

Mito

C

6h

12h

24h

48h

Ifna4 Ifnb1

PBS

DX

MTX

CDDP

Mito

C0

100

150

200


PB

SD

XM

TX

CD

DP

Mito

C

PB

SD

XM

TX

CD

DP

Mito

C

PB

SD

XM

TX

CD

DP

Mito

C

PB

SD

XM

TX

CD

DP

Mito

C

PB

SD

XM

TX

CD

DP

Mito

C

PB

SD

XM

TX

CD

DP

Mito

C

e

Fo

ld c

ha

ng

e

***

***

***

**

***

**

***

***

***

***

*

*

* ***

*** ***

***

***

***

***

***

***

***

***

B16.OVA L1210 S61

0

20

40

60

80

40

80

120

0 0

40

50

60

70

0

5

10

15

20

25160

10

20

30

150

100

5050

6h

12h

24h

48h

***

***

**

***

******

***

***

***

**

***

****

***

***

***

*** *********

***

******

***

***

******

*

***

***

***

Ifna2 Ifna4

PBS

DX

MTX

CDDP

Mito

CPBS

DX

MTX

CDDP

Mito

C

Ifnb1

PBS

DX

MTX

CDDP

Mito

C

Irf7

PBS

DX

MTX

CDDP

Mito

C

0

10

20

30

40

3

6

0 0

2

4

6

0

5

10

15

2076h

12h

24h

48h

***

5

4

2

1***

******

***

***

***

***

***

*

***

***

***

***

***

*** ***

***


4T1

0

**

Cxcl10Irf7

DX

PBS

a

0

20

40

60

80

B16.F10

0

5

10

15

Virus

Co

0

10

20

30

40

50

0

15

30

45**

0

2

4

6

MCA205

NSCLC 2-9

0

10

20

30

Cxcl10

*

b

MDA-MB-231

CXCL10IRF7

c

*

HCC1937

0

CXCL10IRF7

d

1

2

3

4

0

e

0 0

1

2

3

*

0

*

Ifnb1 Cxcl10 Tlr3 Irf7Ifna2


Fo

ld c

ha

ng

eF

old

ch

an

ge

Fo

ld c

ha

ng

e

DX

PBS

DX

PBS

DX

PBS

Ifnb1 Cxcl10 Tlr3 Irf7Ifna2

0

15

30

45

Fo

ld c

ha

ng

eF

old

ch

an

ge

Fo

ld c

ha

ng

e * *

0

20

30

40

3

6

9

*

*

Irf7

2

4

6

8

10*

2

4

6 *

10

0

15

30

45 **

**



WT Tlr3_134 Tlr3_135

104 kDa

38 kDa

Tlr3

Gapdh

Gapdh

37 kDa

38 kDa

Rnasel

Rnasel_26 WT Rnasel_21

Tlr3_206 Tlr3_42


0 5 10 15 20Time (d)

0

100

200

300

400

Tu

mo

r siz

e (

mm

2)

0

100

200

300

400

0

100

200

300

400

0

100

200

300

400a

0 5 10 15 20 25Time (d)

**

PBS

DX

WT Tlr3−/−_42 Tlr3−/−_134 Tlr3−/−_135


0 5 10 15 20 25Time (d)

NS

0 5 10 15 20 25Time (d)

NS

NS

b

0

50

100

150

200

Fo

ld c

ha

ng

e

Cxcl10

0

2

4

6

PBS

DX

Irf7

0

5

10

15

WT

_42 _134 _135

Tlr3−/− WT

_42 _134 _135

Tlr3−/− WT

_42 _134 _135

Tlr3−/−

Ifnb1

**


a

c d

8

6

4

0

2

15.9

±3.78

6

4

0

2

MCA205

***

*****

15

10

5

0

WT_6

***

*****

10

PBS

DX

DX+A

nti-I

fn-αβ

DX+A

nti-I

fnar

1

rIfn-α

10

PBS

DX

DX+A

nti-I

fn-αβ

DX+A

nti-I

fnar

1

rIfn-α

Cxcl1

0 (

ng

ml )

PBS

DX

DX+A

nti-I

fn-αβ

DX+A

nti-I

fnar

1

rIfn-α

20

80

60

40

0

20Ccl5

(n

g m

l )

PBS

100

DX

DX+A

nti-I

fn-αβ

DX+A

nti-I

fnar

1

rIfn-α

0

1,000

2,000

3,000

4,0004T1

0

50

100

150AT3

Cxcl1

0 (p

g m

l ) ###

NSCLC 1-5

Cxcl1

0 (p

g m

l )

0

500

250

750

1,000NSCLC 2-9

0

1,000

500

1,500

2,000

MDA-MB-231

0

5

10

15

20

#

CX

CL

10 (p

g m

l )

*

HCC1937

**

*

0

40

20

60

80

CX

CL

10 (p

g m

l )


NS NS

*** NS NS

###

###

###

*

* * ###

##

***

#

####

###

*

*

##

Ccl5

(n

g m

l )

Cxcl1

0 (

ng

ml )

******

b

NS NS

0.2

5

2.0

0

DX MTXPBS

0.2

5

2.0

0

0.2

5

2.0

0

DX MTXPBS

0.2

5

2.0

0

0.2

5

0.5

0

1.0

0

2.0

0

DX MTXPBS

0.2

5

0.5

0

1.0

0

2.0

0

2 4 8 12

DX MTXPBS

2 4 8 12

2 4 8 12

DX MTXPBS

2 4 8 12

2 4 8 12

DX MTXPBS

2 4 8 12

μMμMμM

μMμMμM

−1

−1 −

1

−1

−1

−1

−1 −

1


Time from randomization (years)

0 2 4 6 8 0 2 4 6 8 0 2 4 6 8

0

20

40

60

80

100

Pro

po

rtio

n (

%)

OS MFS DFS

0 1 2 3 4 5 6 7

497 487 473 446 370 175 53 15

0 1 2 3 4 5 6 7

497 478 446 403 333 156 47 15

0 1 2 3 4 5 6 7

497 473 432 389 320 151 45 14


OS MFS DFS

Number of records 497 497 497

Number of events 48 80 101

Median follow-up 4.87 (4.69; 4.91) 4.66 (4.49; 4.86) 4.57 (4.45; 4.84)

Median survival N/A N/A N/A

Prop @ 2 years 98.56 (97.51; 99.62) 92.60 (90.30; 94.96) 89.54 (86.87; 92.30)

Prop @ 4 years 93.86 (91.68; 96.10) 85.17 (82.02; 88.45) 81.69 (78.27; 85.25)

Prop @ 6 years 85.68 (81.25; 90.34) 81.63 (77.64; 85.83) 75.86 (71.21; 80.81)


0

20

40

60

80

100

2

(19)

3

(37)

4

(39)

5

(59)

6

(53)

7

(17)

8

(13)

0

(90)

MX1 expression

Pro

po

rtio

n o

f T

LR

3 e

xp

ressio

n (

%)



Supplementary Table 1. Transcriptional profile of MCA205 fibrosarcomas treated

with anthracyclines for 48 hours.

Symbol* Description Gene ID* FC

Upregulated

Rsad2 radical S-adenosyl methionine domain containing 2 58185 3.36

LOC100048346 similar to ubiquitin specific protease UBP43 100048346 3.22

I830012O16Rik RIKEN cDNA I830012O16 gene 667370 3.11

LOC100047583 apolipoprotein D-like 100047583 3.04

Cxcl10 chemokine (C-X-C motif) ligand 10 15945 3.01

Ifit3 interferon-induced protein with tetratricopeptide repeats 3 15959 2.97

Irf7 interferon regulatory factor 7 54123 2.76

Cmpk2 cytidine monophosphate (UMP-CMP) kinase 2, mitochondrial 22169 2.72

Usp18 ubiquitin specific peptidase 18 24110 2.67

Isg15 ISG15 ubiquitin-like modifier 100038882 2.66

Oas2 2'-5' oligoadenylate synthetase 2 246728 2.62

Mx2 myxovirus (influenza virus) resistance 2 17858 2.60

Oasl1 2'-5' oligoadenylate synthetase-like 1 231655 2.59

Ifit2 interferon-induced protein with tetratricopeptide repeats 2 15958 2.58

Phf11d PHD finger protein 11D 219132 2.55

LOC100044430 similar to Interferon activated gene 205 100044430 2.48

Dhx58 DEXH (Asp-Glu-X-His) box polypeptide 58 80861 2.48

Trim30 tripartite motif-containing 30A 20128 2.43

Apol9b apolipoprotein L 9b 71898 2.41

Phf11d PHD finger protein 11D 219132 2.26

Ccl5 chemokine (C-C motif) ligand 5 20304 2.24


Gm4951 predicted gene 4951 240327 2.18

Oas1g 2'-5' oligoadenylate synthetase 1G 23960 2.17

Csprs component of Sp100-rs 114564 2.16

AI607873 expressed sequence AI607873 226691 2.12


Cd274 CD274 antigen 60533 2.07

Apol9a apolipoprotein L 9a 223672 2.07


Ly6c1 lymphocyte antigen 6 complex, locus C1 17067 2.06

Gm881 gene model 881 380706 2.06

Daxx Fas death domain-associated protein 13163 2.03

Gpnmb glycoprotein (transmembrane) nmb 93695 2.03

Kcnq1ot1 KCNQ1 overlapping transcript 1 63830 1.99

Znfx1 zinc finger, NFX1-type containing 1 98999 1.98

Plekha4 pleckstrin homology domain containing, family A (phosphoinositide binding specific) member 4

69217 1.97

Samd9l sterile alpha motif domain containing 9-like, transcript variant 1 209086 1.96

Mmp13 matrix metallopeptidase 13 17386 1.94

Il15 interleukin 15 16168 1.91

Gvin1 GTPase, very large interferon inducible 1, transcript variant B 74558 1.91

Dhx58 DEXH (Asp-Glu-X-His) box polypeptide 58 80861 1.89



Cd69 CD69 antigen 12515 1.88

Tgtp T cell specific GTPase 1 21822 1.84

Slfn1 schlafen 1 20555 1.84

Iigp2 immunity-related GTPase family M member 2 54396 1.83

Parp14 poly (ADP-ribose) polymerase family, member 14 547253 1.83

Plac8 placenta-specific 8 231507 1.82

Cdkn1a cyclin-dependent kinase inhibitor 1A (P21) 12575 1.81

Igtp interferon gamma induced GTPase 16145 1.81

Gbp3 guanylate binding protein 3 55932 1.81

Mx1 myxovirus (influenza virus) resistance 1 17857 1.80

Trim34 tripartite motif containing 34 539820 1.79

Slpi secretory leukocyte peptidase inhibitor 20568 1.79

LOC100047963 similar to ADIR1 100047963 1.77

Nt5c3 5'-nucleotidase, cytosolic III 107569 1.76

Trim30d tripartite motif-containing 30D 209387 1.76

Helz2 helicase with zinc finger 2, transcriptional coactivator 22903 1.76

Stat2 signal transducer and activator of transcription 2 20847 1.76

Lgals3bp lectin, galactoside-binding, soluble, 3 binding protein 19039 1.75

Oasl2 2'-5' oligoadenylate synthetase-like 2 23962 1.75


Ube1l ubiquitin-like modifier activating enzyme 7 74153 1.73

Mndal myeloid nuclear differentiation antigen like 100040462 1.73

Isg20 interferon-stimulated protein 57444 1.73


Rnf213 ring finger protein 213 672511 1.73

Irg1 immunoresponsive gene 1 16365 1.72

Casp4 caspase 4, apoptosis-related cysteine peptidase 12363 1.72

Angptl4 angiopoietin-like 4 57875 1.72

Ifi27l2a interferon, alpha-inducible protein 27 like 2A 76933 1.71

H2-Q5 histocompatibility 2, Q region locus 5 15016 1.70

Cxcl1 chemokine (C-X-C motif) ligand 1 14825 1.70

Amy2-2 amylase 2b 545562 1.70

Mnda myeloid cell nuclear differentiation antigen 381308 1.70


Irgm1 immunity-related GTPase family M member 1 15944 1.69

Dtx3l deltex 3-like (Drosophila) 209200 1.68

Bst2 bone marrow stromal cell antigen 2 69550 1.67

Trex1 three prime repair exonuclease 1, transcript variant 2 22040 1.67

Ifnb1 interferon beta 1, fibroblast 15977 1.67

Dennd6b DENN/MADD domain containing 6B 69440 1.66

Parp12 poly (ADP-ribose) polymerase family, member 12 243771 1.66

Agrn agrin 11603 1.66

Eif2ak2 eukaryotic translation initiation factor 2-alpha kinase 2 19106 1.66

Ifi35 interferon-induced protein 35 70110 1.66

Nrap nebulin-related anchoring protein, transcript variant 2 18157 1.65

LOC100044190 hypothetical protein LOC100044190 100044190 1.65

Pydc4 pyrin domain containing 4 623121 1.64

LOC100048556 similar to monocyte chemoattractant protein-5 100048556 1.63

Aftph aftiphilin 216549 1.63


Ddx58 DEAD (Asp-Glu-Ala-Asp) box polypeptide 58 230073 1.63

LOC673501 hypothetical protein LOC673501 673501 1.62

H2-T10 H2-T10 histocompatibility 2, T region locus 10 15024 1.62


Ly6a lymphocyte antigen 6 complex, locus A 110454 1.62

Gch1 GTP cyclohydrolase 1 14528 1.61

Osmr oncostatin M receptor 18414 1.61

H2-T23 histocompatibility 2, T region locus 23 15040 1.60

Xdh xanthine dehydrogenase 22436 1.60

Cd72 CD72 antigen 12517 1.60

Lgals9 lectin, galactose binding, soluble 9 16859 1.59

Trafd1 TRAF type zinc finger domain containing 1 231712 1.58

Pml promyelocytic leukemia, transcript variant 1 18854 1.58

Car13 carbonic anhydrase 13 71934 1.57



Stat1 signal transducer and activator of transcription 1 20846 1.57

Mmp10 matrix metallopeptidase 10 17384 1.56

Ifi205 Ifi205 interferon activated gene 205 226695 1.55

Tdrd7 tudor domain containing 7 100121 1.52


Il13ra1 interleukin 13 receptor, alpha 1 16164 1.51

H2-K2 H2-K2 histocompatibility 2, K region locus 2 630499 1.51

Etnk1 ethanolamine kinase 1 75320 1.51

Psmb9 proteasome (prosome, macropain) subunit, beta type 9 (large multifunctional peptidase 2)

16912 1.51

Ligp1b Iigp1b interferon inducible GTPase 1B 435565 1.50

Ddx60 DEAD (Asp-Glu-Ala-Asp) box polypeptide 60 234311 1.49

Trim21 tripartite motif-containing 21, transcript variant 1 20821 1.48

Adar adenosine deaminase, RNA-specific), transcript variant 1 56417 1.48

Rnf135 ring finger protein 135 71956 1.47

Chi3l3 chitinase 3-like 3 12655 1.47

Nign2 neuroligin 2 216856 1.46

Mitd1 MIT, microtubule interacting and transport, domain containing 1 69028 1.45

Plscr2 phospholipid scramblase 2 18828 1.45

Cited2 Cbp/p300-interacting transactivator, with Glu/Asp-rich carboxy-terminal domain, 2 17684 1.44

Naa20 N(alpha)-acetyltransferase 20, NatB catalytic subunit 67877 1.44

Ms4a6d Ms4a6d membrane-spanning 4-domains, subfamily A, member 6D 68774 1.44


Ogfr opioid growth factor receptor 72075 1.43

Gstt1 glutathione S-transferase theta 1 25260 1.42

Ttc39c Ttc39c tetratricopeptide repeat domain 39C 72747 1.42

Zbp1 Z-DNA binding protein 1 58203 1.42

Lamp2 lysosomal-associated membrane protein 2, transcript variant 1 16784 1.42

Batf2 basic leucine zipper transcription factor, ATF-like 2 74481 1.41

Nfkbiz nuclear factor of kappa light polypeptide gene enhancer in B cells inhibitor, zeta 80859 1.41

Sdc3 syndecan 3 20970 1.41

Ube2l6 ubiquitin-conjugating enzyme E2L 6 56791 1.41

LOC675594 hypothetical LOC675594 675594 1.40

P4ha1 procollagen-proline, 2-oxoglutarate 4-dioxygenase (proline 4-hydroxylase), alpha 1 polypeptide

18451 1.40

Npc2 Niemann Pick type C2 67963 1.40

Lilrb4 leukocyte immunoglobulin-like receptor, subfamily B, member 4 14728 1.40

Sp100 nuclear antigen Sp100 20684 1.40

Sis sucrase isomaltase (alpha-glucosidase) 69983 1.40

Fam46a Fam46a family with sequence similarity 46, member A, transcript variant 2 212943 1.39

Ly6e lymphocyte antigen 6 complex, locus E 17069 1.39

Ftsjd2 Ftsjd2 FtsJ methyltransferase domain containing 2 74157 1.39

Shisa5 shisa homolog 5 (Xenopus laevis), transcript variant 2 66940 1.39

Tcirg1 T cell, immune regulator 1, ATPase, H+ transporting, lysosomal V0 protein A3 27060 1.39

Apol7a Apol7a apolipoprotein L 7a 75761 1.38

H2-Q8 histocompatibility 2, Q region locus 8 15019 1.38

Vcam1 vascular cell adhesion molecule 1 22329 1.38

LOC100046469 similar to Plec1 protein, transcript variant 1 100046469 1.37

Trim26 tripartite motif-containing 26, transcript variant 1 22670 1.37

BC094916 cDNA sequence BC094916 545384 1.37

Sp140 Sp140 nuclear body protein 434484 1.36

Ifi203 interferon activated gene 203, transcript variant 2 15950 1.36


Tor3a Tor3a torsin family 3, member A 30935 1.36

Pde1b phosphodiesterase 1B, Ca2+-calmodulin dependent 18574 1.36

Trpm6 transient receptor potential cation channel, subfamily M, member 6 225997 1.36

Psmb10 proteasome (prosome, macropain) subunit, beta type 10 19171 1.36


Mlkl mixed lineage kinase domain-like 74568 1.36

Fcgr1 Fc receptor, IgG, high affinity I 14129 1.34

3300005D01Rik RIKEN cDNA 3300005D01 gene 78512 1.34

LOC100047261 similar to spermidine/spermine N1-acetyltransferase 100047261 1.34

Pla1a phospholipase A1 member A 85031 1.33

Lamc2 laminin, gamma 2 16782 1.33

Cd40 CD40 antigen, transcript variant 5 21939 1.33

P2rx4 purinergic receptor P2X, ligand-gated ion channel 4 18438 1.33

Wdf1 WD repeat and FYVE domain containing 1 69368 1.32

Trp53inp2 transformation related protein 53 inducible nuclear protein 2 68728 1.32

Oas1a 2'-5' oligoadenylate synthetase 1G 23960 1.32

Cutc cutC copper transporter homolog (E.coli) 66388 1.31

Tor1aip1 torsin A interacting protein 1 208263 1.31

Arsj arylsulfatase J 271970 1.31

P2ry14 purinergic receptor P2Y, G-protein coupled, 14 140795 1.31

Scimp Scimp SLP adaptor and CSK interacting membrane protein 327957 1.31

Otud5 OTU domain containing 5 54644 1.31

Fam162a Fam162a family with sequence similarity 162, member A 70186 1.30

Sdc4 syndecan 4 20971 1.30

Wsb1 WD repeat and SOCS box-containing 1, transcript variant 2 78889 1.30

Tnfrsf11b tumor necrosis factor receptor superfamily, member 11b (osteoprotegerin) 18383 1.29

H2-M3 histocompatibility 2, M region locus 3 14991 1.29

Hdac5 histone deacetylase 5, transcript variant 1 15184 1.29

Lst1 leukocyte specific transcript 1 16988 1.28

Idb2 Id2 inhibitor of DNA binding 2 15902 1.28

Il7r interleukin 7 receptor 16197 1.28

Grn granulin 14824 1.28

Clk4 CDC like kinase 4 12750 1.27

Oas1b 2'-5' oligoadenylate synthetase 1B 23961 1.27

Cask calcium/calmodulin-dependent serine protein kinase (MAGUK family) 12361 1.26

Cd180 CD180 antigen 17079 1.25

Zfp281 zinc finger protein 281 226442 1.25

Cp ceruloplasmin, transcript variant 1 12870 1.24


Klhl26 kelch-like 26, transcript variant 1 234378 1.24

Ltbp3 latent transforming growth factor beta binding protein 3 16998 1.24

9530068E07Rik RIKEN cDNA 9530068E07 gene 213673 1.24

Lrpap1 low density lipoprotein receptor-related protein associated protein 1 16976 1.24

Vopp1 Vopp1 vesicular, overexpressed in cancer, prosurvival protein 1 232023 1.23

Sdcbp syndecan binding protein 53378 1.22

Downregulated

Heatr1 HEAT repeat containing 1 217995 −1.24

Dph3 DPH3 homolog (KTI11, S. cerevisiae), transcript variant 2 105638 −1.24

Agl amylo-1,6-glucosidase, 4-alpha-glucanotransferase 77559 −1.24

Frmd4a FERM domain containing 4A 209630 −1.24

Qk Qk quaking 19317 −1.25

Slc48a1 Slc48a1 solute carrier family 48 (heme transporter), member 1 67739 −1.25

Mrps18b mitochondrial ribosomal protein S18B 66973 −1.25

H2afz H2A histone family, member Z 51788 −1.25

LOC100043671 hypothetical protein LOC100043671 100043671 −1.25

Nob1 NIN1/RPN12 binding protein 1 homolog (S. cerevisiae) 67619 −1.26

Fpgs folylpolyglutamyl synthetase 14287 −1.26

Ddx27 DEAD (Asp-Glu-Ala-Asp) box polypeptide 27 228889 −1.26

Mogs Mogs mannosyl-oligosaccharide glucosidase 57377 −1.27

Fam78a Fam78a family with sequence similarity 78, member A 241303 −1.27

Banf1 barrier to autointegration factor 1, transcript variant 2 23825 −1.28

Nap1l1 nucleosome assembly protein 1-like 1 53605 −1.28

Klhl6 kelch-like 6 239743 −1.28

Abcc4 ATP-binding cassette, sub-family C (CFTR/MRP), member 4 239273 −1.28

Srm spermidine synthase 20810 −1.28

Raly hnRNP-associated with lethal yellow 19383 −1.29

Cyb5b cytochrome b5 type B 66427 −1.29

Srrt serrate RNA effector molecule homolog (Arabidopsis) 83701 −1.29

Gar1 GAR1 ribonucleoprotein homolog (yeast) 68147 −1.29

Klf2 Kruppel-like factor 2 (lung) 16598 −1.29

Ptp4a2 protein tyrosine phosphatase 4a2 19244 −1.29

Mir17hg Mir17hg Mir17 host gene 1 (non-protein coding) 75957 −1.30


Prep prolyl endopeptidase 19072 −1.30

Exosc1 exosome component 1 66583 −1.30

Hist1h2ai histone cluster 1, H2ai 319191 −1.30

Myof myoferlin, transcript variant 1 226101 −1.30

Gusb glucuronidase, beta 110006 −1.31

Nrp1 neuropilin 1 18186 −1.31

4933411D12Rik RIKEN cDNA 4933411D12 gene 74086 −1.31

Aoc3 amine oxidase, copper containing 3 11754 −1.31

Cotl1 coactosin-like 1 (Dictyostelium) 72042 −1.32

Dctd dCMP deaminase 320685 −1.33

Slc12a2 solute carrier family 12, member 2 20496 −1.33

Rangrf RAN guanine nucleotide release factor 577885 −1.33

St6gal1 beta galactoside alpha 2,6 sialyltransferase 1 20440 −1.34

Gatc Gatc glutamyl-tRNA(Gln) amidotransferase, subunit C homolog (bacterial) 384281 −1.35

Rassf4 Ras association (RalGDS/AF-6) domain family member 4 213391 −1.35

Slc35c2 solute carrier family 35, member C2 228875 −1.36

Rrp12 ibosomal RNA processing 12 homolog (S. cerevisiae) 107094 −1.36

Hist2h2ab histone cluster 2, H2ab 621893 −1.36

Ppat phosphoribosyl pyrophosphate amidotransferase, transcript variant 8 231327 −1.36

Adamts2 a disintegrin-like and metallopeptidase (reprolysin type) with thrombospondin type 1 motif, 2

216725 −1.37

Shmt2 serine hydroxymethyltransferase 2 (mitochondrial) 108037 −1.37

Iars isoleucine-tRNA synthetase 105148 −1.37

Sqle squalene epoxidase 20775 −1.38

Psat1 phosphoserine aminotransferase 1 107272 −1.38

Elovl1 elongation of very long chain fatty acids (FEN1/Elo2, SUR4/Elo3, yeast)-like 1, transcript variant 2

54325 −1.39

Sfxn1 sideroflexin 1 14057 −1.40

Emb embigin 13723 −1.41

Scd1 stearoyl-Coenzyme A desaturase 1 20249 −1.42

Grb10 growth factor receptor bound protein 10 14783 −1.42

ELOVL6 ELOVL family member 6, elongation of long chain fatty acids (yeast) 170439 −1.44

P2ry6 pyrimidinergic receptor P2Y, G-protein coupled, 6 233571 −1.44

Ncl nucleolin 17975 −1.45

LOC100047619 similar to solute carrier family 7 (cationic amino acid transporter, y+ system), member 5 100047619 −1.45


Asns asparagine synthetase 27053 −1.46

Stra6 stimulated by retinoic acid gene 6 20897 −1.48

Btbd11 BTB (POZ) domain containing 11, transcript variant 2 74007 −1.50

Xpot exportin, tRNA (nuclear export receptor for tRNAs) 73192 −1.53

Lrrc15 leucine rich repeat containing 15 74488 −1.62

Tfrc transferrin receptor 22042 −1.72

Igfbp5 insulin-like growth factor binding protein 5 16011 −1.76

Mrc1 mannose receptor, C type 1 17533 −2.01

Hbb-b1 hemoglobin, beta adult major chain 15129 −2.48

Abbreviations: FC, fold change. *source http://www.ncbi.nlm.nih.gov/gene/.


Supplementary Table 2. Patient characteristics.

Parameter pCR (n = 24) RD (n = 26) P

Age

Median (range) 50 (32−75) 48 (32−67) 0.45

Clinical stage

cT1−cT2 12 (50.0%) 17 (65.0%) 0.42

cT3−cT4 12 (50.0%) 9 (35.0%)

Histological grade

II 4 (17.0%) 12 (46.0%)

0.12 III 18 (75.0%) 14 (54.0%)

Unknown 2 (8.0%) 0

Estrogen Receptor status*

Negative 16 (67.0%) 16 (62.0%)

0.87 Positive 8 (33.0%) 7 (27.0%)

Unknown 0 3 (11.0%)

ESR1 expression**

Negative 19 (79.0%) 19 (73.0%) 0.86

Positive 5 (21.0%) 7 (27.0%)

ERBB2 expression***

Normal 18 (75.0%) 16 (62.0%) 0.4

High 6 (25.0%) 10 (38.0%)

Abbreviations: ESR1, estrogen receptor 1; pCR, pathological complete response; RD, residual disease. *as determined by

immunohistochemistry (cut-off: 10% stained cells) or ligand-binding assay (10 fmol mg−1); **Affymetrix U133A, ESR1 probe

205225_at, cut-off for positivity: 500; ***Affymetrix U133A, ERBB2 probe 216836_s_at, cut-off for positivity: 1125.


Supplementary Table 3. Association between metagenes (biological processes) and pathological complete response to

anthracycline-based chemotherapy.

Representative gene

Functional annotation

Overall population (n = 50) ER-negative population* (n = 38)

AUC 95% CI P** BH P AUC 95% CI P** BH P

MX1 Interferon 0.72 (0.57−0.86) 0.004 0.03 0.74 (0.57−0.89) 0.004 0.04

TPX2 Proliferation 0.71 (0.55−0.85) 0.007 0.03 0.68 (0.50−0.86) 0.03 0.11

ESR1 Luminal-basal 0.36 (0.20−0.52) 0.07 0.17 0.30 (0.14−0.49) 0.04 0.11

CLCA2 Apocrine 0.36 (0.21−0.52) 0.08 0.17 0.30 (0.14−0.49) 0.05 0.11

ADM Hypoxia 0.54 (0.38−0.70) 0.61 0.78 0.53 (0.34−0.72) 0.73 0.89

FABP4 Adipocyte 0.46 (0.30−0.63) 0.64 0.78 0.47 (0.28−0.67) 0.77 0.89

DCN Stroma 0.46 (0.30−0.63) 0.67 0.78 0.47 (0.28−0.66) 0.78 0.89

GZMA T cell 0.53 (0.36−0.69) 0.75 0.78 0.48 (0.29−0.68) 0.89 0.89

CD83 B cell 0.52 (0.36−0.69) 0.78 0.78 0.48 (0.29−0.68) 0.89 0.89

Abbreviations: AUC, area under the ROC curve; BH, Benjamini & Hochberg procedure; CI, confidence interval. *based on ESR1 mRNA expression, as determined by microarray analyses,

Affymetrix U133A, ESR1 probe 205225_at, cut-off for positivity: 500; **2-sided bootstrap P value.


1

Supplementary Table 4. Patient stratification according to MX1 expression.

Parameter All

(n = 743) MX1 low (n = 650)

MX1 high (n = 93) P

Age

< 50 180 (24.2%) 158 (87.8%) 22 (12.2%) 1

≥ 50 563 (75.8%) 492 (87.4%) 71 (12.6%)

Tumor size (mm) ≤ 20 412 (55.5%) 370 (89.8%) 42 (10.2%)

0.05 > 20 325 (43.7%) 275 (84.6%) 50 (15.4%)

Unknown 6 (0.8%) 5 (83.0%) 1 (17.0%)

Histological grade 1−2 510 (68.6%) 459 (90.0%) 51 (10.0%)

0.002 3 227 (30.6%) 185 (81.5%) 42 (18.5%)

Unknown 6 (0.8%) 6 (100.0%) 0

Lymph node status Negative 426 (57.3%) 369 (86.6%) 57 (13.4%)

0.5 Positive 317 (42.7%) 281 (88.6%) 36 (11.4%)

Estrogen Receptor status*

< 10 fmol mg−1 89 (12.0%) 67 (75.3%) 22 (24.7%)

0.0003 ≥ 10 fmol mg−1 559 (75.2%) 501 (89.6%) 58 (10.4%)

Unknown 95 (12.8%) 82 (86.0%) 13 (14.0%)

Adjuvant chemotherapy None 370 (49.8%) 320 (86.5%) 50 (13.5%)

0.5 Anthracycline-based 373 (50.2%) 330 (88.5%) 43 (11.5%)

Abbreviations: MX1, myxovirus resistance 1. *as determined by ligand-binding assay.


Supplementary Table 5. Interaction of MX1 Allred score with clinical parameters.

Parameter MX1 low (n = 377)

MX1 high (n = 110) Odds Ratio LRT

Arm

1 182 (48.3%) 59 (53.6%) 1 0.97; P < 0.3239

2 195 (51.7%) 51 (46.4%) 0.808 [0.528;1.234]

Estrogen Receptor

Negative 95 (25.2%) 35 (31.8%) 1 1.92; P < 0.1654

Positive 282 (74.8%) 75 (68.2%) 0.719 [0.455;1.149]

Progesteron Receptor

Negative 124 (32.9%) 44 (40.4%) 1

1.94; P < 0.1635 Positive 250 (66.3%) 65 (59.6%) 0.732 [0.473;1.137]

Unknown 3 (0.8%) 1 (0.9%) -

ERBB2

Negative 263 (69.8%) 74 (67.3%) 1 0.27; P < 0.6048

Positive 114 (30.2%) 36 (32.7%) 1.127 [0.712;1.764]

Tumor Subtype

Luminal 234 (62.1%) 59 (53.6%) 1

4.02; P < 0.1339 ERBB2+ 114 (30.2%) 36 (32.7%) 1.279 [0.795;2.038]; P < 0.3074

Triple negative 28 (7.4%) 14 (12.8%) 2.005 [0.981;3.961]; P < 0.0562

Unknown 1 (0.3%) 1 (0.9%) -

SBR

0−I 64 (17.0%) 8 (7.3%) 1

13.87; P < 0.0010 II 170 (45.1%) 40 (36.4%) 1.802 [0.851;4.234]; P < 0.1279

III 140 (37.1%) 61 (55.4%) 3.322 [1.603;7.694]; P < 0.0008

Unknown 3 (0.8%) 1 (0.9%) -

Trastuzumab

Yes 46 (12.2%) 13 (11.8%) 1 0; P < 0.9686

No 331 (87.8%) 97 (88.2%) 1.013 [0.544;2.001]

Age

≤ 40 40 (10.6%) 15 (13.6%) 1

4.08; P < 0.2531 40−50 122 (32.4%) 42 (38.2%) 0.907 [0.464;1.829]; P < 0.7785

50−60 153 (40.6%) 42 (38.2%) 0.723 [0.372;1.453]; P < 0.3546

> 60 62 (16.4%) 11 (10%) 0.481 [0.2;1.128]; P < 0.0925

Menopausal status

No 116 (30.8%) 34 (30.9%) 1 0.85; P < 0.3558 Yes 145 (38.4%) 33 (30%) 0.777 [0.455;1.328]

Unknown 116 (30.8%) 43 (39.1%) - Ganglion

≤ 3 266 (70.6%) 79 (71.8%) 1

0.05; P < 0.9757 (3−9) 83 (22.0%) 23 (20.9%) 0.943 [0.551;1.571]; P < 0.8264

> 9 28 (7.4%) 8 (7.3%) 1 [0.422;2.154]; P < 0.9996

Tumor

≤ 20 184 (48.8%) 53 (48.2%) 1

0.07; P < 0.9666 20−50 164 (43.5%) 49 (44.5%) 1.038 [0.667;1.612]; P < 0.8690

> 50 26 (6.9%) 8 (7.3%) 1.106 [0.457;2.452]; P < 0.8130

Unknown 3 (0.8%) 0 - Prognosis

Good 150 (39.8%) 33 (30.0%) 1

3.69; P < 0.0547 Poor 224 (59.4%) 77 (70.0%) 1.551 [0.991;2.467] Unknown 3 (0.8%) 0 -

Abbreviations: LRT, likelihood ratio test.


Supplementary Table 6. Analysis of the predictive value of TLR3 for response to

chemotherapy.

Comparison 4 levels 0 vs. 1+ 0−2 vs. 3+

Overall Survival

TLR3 Allred score 0.20; P < 0.9777 0.20; P < 0.657 0.21; P < 0.6485

Prognosis group 6.92; P < 0.0085 6.94; P < 0.0084 6.88; P < 0.0087

Interaction 0.47; P < 0.9253 0.05; P < 0.8184 0.07; P < 0.7860

Poor 0.34; P < 0.9527 0.04; P < 0.8377 0.01; P < 0.9091

Good 0.18; P < 0.9803 0.05; P < 0.8187 0.16; P < 0.6898

Metastasis-free survival


Prognosis group 10.8; P < 0.0010 10.63; P < 0.0011 10.58; P < 0.0011

Interaction 4.46; P < 0.2159 0.57; P < 0.4491 1.87; P < 0.1719

Poor 4; P < 0.2611 0.5; P < 0.4808 2.11; P < 0.1462

Good 1.17; P < 0.7607 0.03; P < 0.8616 0; P < 0.9844

Disease-free survival


Prognosis group 17.63; P <<1e-04 16.99; P <<1e−04 16.94; P <<1e−04

Interaction 3.46; P < 0.3265 0.2; P < 0.6524 0.72; P < 0.3969

Poor 3.71; P < 0.2945 0.26; P < 0.6100 1.67; P < 0.1959

Good 2.83; P < 0.4186 0; P < 0.9580 0.63; P < 0.4263

Abbreviations: TLR3, Toll-like receptor 3.


1

Supplementary Figure Legends

Supplementary Figure 1. Type I interferon signature in neoplastic lesions exposed to

anthracycline-based chemotherapy. a−e. Levels of interferon-stimulated gene (ISG) transcripts in

anthracycline-treated fibrosarcomas. MCA205 fibrosarcomas (a−c) or methylcholanthrene (MCA)-

driven sarcomas (d) established in immunocompetent C57Bl/6 mice (n = six per group) were treated

with PBS or a single intratumoral injection of doxorubicin (DX), collected after the indicated time and

processed for the assessment of ISG products by quantitative RT-PCR upon the cytofluorometric

separation of CD45− (a,d), CD45+ (b), CD3−CD19−CD11b+Ly6G+ (c), CD3−CD19−CD11b+Ly6Chigh (c),

and CD3−CD19−CD11b+Ly6Clow (c) cells. Alternatively, MCA205 fibrosarcoma cells recovered from

tumors or maintained in culture were exposed to PBS or oxaliplatin (OXP) for 48 hrs, then processed as

in a−d for the quantification of Ifnb1 levels. Data are reported as mean fold changes ± SD, upon intra-

sample normalization to the levels of Ppia. NS, non significant, *P < 0.05, **P < 0.01, ***P < 0.001

(unpaired Student’s t test), as compared to PBS-treated cells of the same type. A representative

experiment containing six tumors per group, out of two yielding similar results, is depicted.

Supplementary Figure 2. Cancer cell-autonomous role of IFNAR in the efficacy of anthracycline-

based chemotherapy. a. Role of IFNAR in chemotherapeutic responses to anthracyclines. Wild-type

(WT) and Ifnar1−/− MCA205 fibrosarcomas established in WT C57Bl/6 mice (n = ten per group) were

treated with PBS or a single intratumoral injection of doxorubicin (DX). Tumor growth is reported as

mean tumor surface ± SEM over time. NS, non significant, **P < 0.01, (unpaired Student’s t test), as

compared to PBS-treated tumors. b,c. Role of IFNAR in CXCL10 release and MHC Class I expression

by cancer cells. WT and Ifnar1−/− MCA205 fibrosarcoma cells were exposed to PBS, DX, recombinant

Ifn-α1 (rIfn-α), or recombinant Ifn-γ (rIfn-γ) for 48 hrs, followed by the quantification of Cxcl10 in

culture supernatants by ELISA, b) or the assessment of MHC Class I expression levels on the cell


2

surface (by cytofluorometry by specific antibodies, c). Data are reported as mean ng ml−1 or mean

fluorescence intensity (MFI), respectively, ± SD. NS, non significant, *P < 0.05, **P < 0.01, ***P <

0.001 (unpaired Student’s t test), as compared to PBS-treated cells.

Supplementary Figure 3. Effects of chemotherapy on the type I interferon signature. a. Cytotoxic

activity of chemotherapy on murine sarcomas. Wild-type (WT) MCA205 fibrosarcoma cells as well as

methylcholanthrene (MCA)-driven sarcoma cells of the indicated genotype were treated with PBS,

doxorubicin (DX), mitoxantrone (MTX), cisplatin (CDDP) or mitomycin C (MitoC) for 24 hrs, then

processed for the cytofluorometric assessment of cell death-associated parameters upon AnnexinV-

DAPI co-staining. Black and white columns depicts the percentage of dead (DAPI+) or dying

(DAPI−AnnV+) cells. Data are reported as mean percentages ± SD. b−e. Effects of chemotherapy on

interferon-stimulated gene (ISG) products. MCA205 fibrosarcoma cells (b), MCA-driven sarcoma cells

of the indicated genotype (c), murine ovalbumin-expressing B16 (B16.OVA) melanoma cells (d) and

murine L1210S61 leukemia (e) cells were exposed to PBS or sublethal doses of DX, MTX, CDDP or

MitoC for the indicated time, followed by the assessment of ISG products by quantitative RT-PCR.

Data are reported as mean fold changes ± SD, upon intra-sample normalization to the levels of Ppia.

Results are from one representative experiment out of at least two performed yielding similar results.

Supplementary Figure 4. Type I interferon transcriptional fingerprint in m urine and human

epithelial cancer cell lines exposed to chemotherapy or oncolytic viruses. a−d. Effects of

chemotherapy on interferon-stimulated gene (ISG) products. Mouse 4T1 mammary carcinoma cells (a),

mouse 2-9 non-small cell lung cancer (NSCLC) cells (b) as well as human MDA-MB-231 and

HCC1937 mammary carcinoma (c,d) were exposed to PBS or sublethal doses of doxorubicin (DX) for

24 hrs, followed by the assessment of ISG products by quantitative RT-PCR. (e) Effects of oncolytic

viruses on ISG products. Murine fibrosarcoma MCA205 cells (upper panels) or murine B16.F10


3

melanoma cells (lower panels) were exposed to PBS or WR oncolytic vaccinia virus (at a multiplicity

of infection of 1 × 10−1, which results in 15% cell death and > 90% infectivity, (data not shown) for 24

hrs, then processed as in a−d. Data are reported as mean fold changes ± SD, upon intra-sample

normalization to the levels of Ppia. Results are from one representative experiment out of two

performed yielding similar results. *P < 0.05, **P < 0.01, ***P < 0.001 (unpaired Student’s t test), as

compared to PBS-treated cells.

Supplementary Figure 5. Western blotting of utilized tumor cell clones. Wild-type (WT) MCA205

fibrosarcoma cells, the indicated MCA205 cell clones deleted of Tlr3 by means of a specific zinc-finger

nuclease as well as methylcholanthrene (MCA)-driven sarcoma cells of the indicated genotype were

processed for the immunoblotting-assisted assessment of Tlr3 and Rnasel, as relevant. Glyceraldehyde-

3-phosphate dehydrogenase (Gapdh) levels were monitored to ensure equal lane loading. Results are

from one representative experiments out of two performed yielding similar results.

Supplementary Figure 6. Impact of TLR3 on the type I interferon transcripti onal fingerprint

induced by anthracyclines. a. Role of TLR3 on the efficacy of anthracycline-based chemotherapy.

Wild-type (WT) and Tlr3−/− MCA205 fibrosarcomas established in WT C57Bl/6 mice (n = ten per

group) were treated with PBS or a single intratumoral injection of doxorubicin (DX). Tumor growth is

reported as mean tumor surface ± SEM over time. NS, non significant, **P < 0.01, (unpaired Student’s

t test), as compared to PBS-treated tumors. b. Effect of TLR3 on anthracycline-responsive interferon-

stimulated gene (ISG) products. WT and Tlr3−/− MCA205 fibrosarcoma cells were exposed to PBS or

DX for 24 hrs, followed by the assessment of ISG products by quantitative RT-PCR. Data are reported

as mean fold changes ± SD, upon intra-sample normalization to the levels of Ppia. Results are from

one representative experiment out of two performed yielding similar results. *P < 0.05 (unpaired

Student’s t test), as compared to PBS-treated cells of the same type.


4

Supplementary Figure 7. CXCL10 release by mouse and human cancer cell lines responding

anthracyclines. a,b. Release of Cxcl10 by murine sarcoma cells exposed to doxorubicin (DX). Wild-

type (WT) MCA205 fibrosarcoma cells (a) as well as WT methylcholanthrene (MCA)-driven sarcoma

cells (b) were exposed to PBS, DX or recombinant Ifn-α1 (rIfn-α), alone or in the presence of Ifn-αβ-

or Ifnar1-neutralizing antibodies, for 24 hrs, followed by the assessment of Cxcl10 and Ccl5 in culture

supernatants by ELISA. NS, non significant, *P < 0.05, **P < 0.01, ***P < 0.001 (unpaired Student’s t

test), as compared to PBS-treated cells. c,d. Release of CXCL10 by mammary carcinoma and non-small

cell lung carcinoma (NSCLC) cells exposed to DX or mitoxantrone (MTX). Murine AT3 and 4T1

mammary carcinoma cells (upper panels), murine 1-5 and 2-9 non-small cell lung cancer cells (lower

panels) and human MDA-MB-231 mammary carcinoma cells (d) were exposed to PBS or increasing

concentrations (2−12 µM) of DX or MTX for 24 hrs, followed by the assessment of CXCL10 in culture

supernatants by ELISA. Data are reported as mean ng ml−1 or pg ml−1 ± SD. NS, non significant, *P <

0.05, **P < 0.01, ***P < 0.001 (unpaired Student’s t test), as compared to PBS with DX-treated cells,

#P < 0.05, ##P < 0.01, ###P < 0.001 (unpaired Student’s t test), as compared to PBS with MTX-treated

cells.

Supplementary Figure 8. Clinical evolution of breast carcinoma patients enrolled in the PACS04

clinical trial. The overall survival (OS), metastasis-free-survival (MFS) and disease-free survival

(DFS) and of n = 497 breast carcinoma patients enrolled in PACS04 clinical trials are plotted according

to the Kaplan-Meier method. Number of patients at risk over time, number of events in the observation

period, median follow-up and the probability of being alive, metastasis-free or disease-free 2, 4 and 6

years after randomization are reported. Of note, only 487 patients could be scored with accuracy by

pathologists for MX1 expression as reported in Fig. 6d−f.


5

Supplementary Figure 9. Correlation between MX1 and TLR3 expression levels in breast

carcinoma patients. TLR3 and MX1 expression levels were quantified as Allred scores upon the

immunohistochemical staining of tumor tissue microarrays from n = 327 early breast carcinoma

patients presenting with nodal involvement in the context of the PACS04 Phase III clinical trial

(NCT00054587) for which both TLR3 and MX1 could be quantified. The percentage of neoplastic

lesions expressing TLR3 (Allred score > 0) is reported upon the stratification of patients based on MX1

Allred scores. The number of patients in each stratum is indicated. Supplementary Table 6 reports the

predictive value of TLR3 expression in these patients.


a b cd45+ - nature · rsad2 radical s-adenosyl methionine domain containing 2 58185 3.36...

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