IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell

作者：Lulu Shao, Weizhou Hou, Nicole E. Scharping, Frank P. Vendetti, Rashmi Srivastava, Chandra Nath Roy, Ashley V. Menk, Yiyang Wang, Joë-Marc Chauvin, Pooja Karukonda, Stephen H. Thorne, Veit Hornung, Hassane M. Zarour, Christopher J. Bakkenist, Greg M. Delgoffe, Saumendra N. Sarkar · 发表于：Cancer Immunology Research · 年份：2019 · DOI：10.1158/2326-6066.cir-18-0711 · 被引用次数：91 · 研究领域：Cancer Immunotherapy and Biomarkers、Cancer, Stress, Anesthesia, and Immune Response、Immune Cell Function and Interaction

Abstract 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.