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 |
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Faculties: | Chemistry and Pharmacy > Department of Biochemistry |
Subjects: | 500 Science > 540 Chemistry |
ISSN: | 2326-6066 |
Language: | English |
Item ID: | 83517 |
Date Deposited: | 15. Dec 2021, 15:08 |
Last Modified: | 15. Dec 2021, 15:08 |