Anti-tumor immunity influences cancer cell reliance upon ATG7.

Michael D Arensman, Xiaoran S Yang, Wenyan Zhong, Stephanie Bisulco, Erik Upeslacis, Edward C Rosfjord, Shibing Deng, Robert T Abraham, Christina H Eng

Oncoimmunology 2020 Aug 23

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Macroautophagy (autophagy) is an essential cellular catabolic process required for survival under conditions of starvation. The role of autophagy in cancer is complex, context-dependent and at times contradictory, as it has been shown to inhibit, promote or be dispensable for tumor progression. In this study, we evaluated the contribution of the immune system to the reliance of tumors on autophagy by depleting autophagy-related 7 (ATG7) in murine tumor cells and grafting into immunocompetent versus immunodeficient hosts. Although loss of ATG7 did not affect tumor growth in vitro or in immunodeficient mice, our studies revealed that cancer cell reliance on autophagy was influenced by anti-tumor immune responses, including those mediated by CD8+ T cells. Furthermore, we provide insights into possible mechanisms by which autophagy disruption can enhance anti-tumor immune responses and suggest that autophagy disruption may further benefit patients with immunoreactive tumors. © 2020 Pfizer. Published with license by Taylor & Francis Group, LLC.

Citation

Michael D Arensman, Xiaoran S Yang, Wenyan Zhong, Stephanie Bisulco, Erik Upeslacis, Edward C Rosfjord, Shibing Deng, Robert T Abraham, Christina H Eng. Anti-tumor immunity influences cancer cell reliance upon ATG7. Oncoimmunology. 2020 Aug 23;9(1):1800162