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.