RT Journal Article
SR Electronic
T1 IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell
JF Cancer Immunology Research
JO Cancer Immunol Res
FD American Association for Cancer Research
SP 1258
OP 1266
DO 10.1158/2326-6066.CIR-18-0711
VO 7
IS 8
A1 Shao, Lulu
A1 Hou, Weizhou
A1 Scharping, Nicole E.
A1 Vendetti, Frank P.
A1 Srivastava, Rashmi
A1 Roy, Chandra Nath
A1 Menk, Ashley V.
A1 Wang, Yiyang
A1 Chauvin, Joe-Marc
A1 Karukonda, Pooja
A1 Thorne, Stephen H.
A1 Hornung, Veit
A1 Zarour, Hassane M.
A1 Bakkenist, Christopher J.
A1 Delgoffe, Greg M.
A1 Sarkar, Saumendra N.
YR 2019
UL http://cancerimmunolres.aacrjournals.org/content/7/8/1258.abstract
AB Multiple studies have associated the transcription factor IRF1 with tumor-suppressive activities. Here, we report an opposite tumor cell–intrinsic function of IRF1 in promoting tumor growth. IRF1-deficient tumor cells showed reduced tumor growth in MC38 and CT26 colon carcinoma and B16 melanoma mouse models. This reduction in tumor growth was dependent on host CD8+ T cells. Detailed profiling of tumor-infiltrating leukocytes did not show changes in the various T-cell and myeloid cell populations. However, CD8+ T cells that had infiltrated IRF1-deficieint tumors in vivo exhibited enhanced cytotoxicity. IRF1-deficient tumor cells lost the ability to upregulate PD-L1 expression in vitro and in vivo and were more susceptible to T-cell–mediated killing. Induced expression of PD-L1 in IRF1-deficient tumor cells restored tumor growth. These results indicate differential activity of IRF1 in tumor escape.