IRF1 inhibits antitumor immunity through the upregulation of PD-L1 in the tumor cell: Tumor promoting activity of IRF1

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 e xhibited 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.