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.
- Received October 4, 2018.
- Revision received March 29, 2019.
- Accepted June 19, 2019.
- Copyright ©2019, American Association for Cancer Research.
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Published OnlineFirst June 25, 2019
doi: 10.1158/2326-6066.CIR-18-0711
