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

Shao, Lulu; Hou, Weizhou; Scharping, Nicole E.; Vendetti, Frank P.; Srivastava, Rashmi; Roy, Chandra Nath; Menk, Ashley V.; Wang, Yiyang; Chauvin, Joe-Marc; Karukonda, Pooja; Thorne, Stephen H.; Hornung, Veit; Zarour, Hassane M.; Bakkenist, Christopher J.; Delgoffe, Greg M. and Sarkar, Saumendra N. (2019): IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell. In: Cancer Immunology Research, Vol. 7, No. 8: pp. 1258-1266

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 thorn T cells. Detailed profiling of tumor-infiltrating leukocytes did not show changes in the various T-cell and myeloid cell populations. However, CD8 thorn 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.

• Item Type: Journal article
• Faculties: Chemistry and Pharmacy > Department of Biochemistry
• Subjects: 500 Science > 540 Chemistry
• ISSN: 2326-6066
• Language: English