Research ArticleTUMOR IMMUNOLOGY

Autophagy protects tumors from T cell–mediated cytotoxicity via inhibition of TNFα-induced apoptosis

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Science Immunology  18 Dec 2020:
Vol. 5, Issue 54, eabb9561
DOI: 10.1126/sciimmunol.abb9561

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Autophagy protects tumors from T cells

Tumors evade antitumor T cells by various mechanisms. Young et al. used a CRISPR screen to identify that TNFα and autophagy play a role in T cell–mediated killing of tumor cells. Pharmacologic or genetic (CRISPR knockout of Rb1cc1) inhibition of autophagy in tumor cells increased TNFα-mediated T cell killing of tumor cells. Rb1cc1 knockout in tumor cells improved the efficacy of immune checkpoint blockade in a mouse tumor model. However, CRISPR knockout of the TNFα receptor in tumor cells partially abrogated the improved efficacy of immune checkpoint blockade in the absence of Rb1cc1. Thus, autophagy inhibition may improve T cell–mediated immunotherapies in patients with cancer.

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