American Association for Cancer Research
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Figure S3 from IRF1 Inhibits Antitumor Immunity through the Upregulation of PD-L1 in the Tumor Cell

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posted on 2023-04-04, 00:42 authored by Lulu Shao, Weizhou Hou, Nicole E. Scharping, Frank P. Vendetti, Rashmi Srivastava, Chandra Nath Roy, Ashley V. Menk, Yiyang Wang, Joe-Marc Chauvin, Pooja Karukonda, Stephen H. Thorne, Veit Hornung, Hassane M. Zarour, Christopher J. Bakkenist, Greg M. Delgoffe, Saumendra N. Sarkar

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ARTICLE 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.

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    Cancer Immunology Research

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    Keywords

    Cell SignalingGastrointestinal CancersColorectal cancerGene RegulationMechanisms of transcriptionImmunologyImmunomodulationSkin CancersMelanoma

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