Journal
NATURE CANCER
Volume 2, Issue 10, Pages 1018-+Publisher
NATURE PORTFOLIO
DOI: 10.1038/s43018-021-00263-z
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The study identified tumoral ring finger protein 2 as a negative regulator of antitumor immunity in various human cancers, deletion of related genes can induce durable tumor rejection and establish immune memory.
Expanding the utility of immune-based cancer treatments is a clinical challenge due to tumor-intrinsic factors that suppress the immune response. Here we report the identification of tumoral ring finger protein 2 (RNF2), the core subunit of polycomb repressor complex 1, as a negative regulator of antitumor immunity in various human cancers, including breast cancer. In syngeneic murine models of triple-negative breast cancer, we found that deleting genes encoding the polycomb repressor complex 1 subunits Rnf2, BMI1 proto-oncogene, polycomb ring finger (Bmi1), or the downstream effector of Rnf2, remodeling and spacing factor 1 (Rsf1), was sufficient by itself to induce durable tumor rejection and establish immune memory by enhancing infiltration and activation of natural killer and CD4(+) T cells, but not CD8(+) T cells, into the tumor and enabled their cooperativity. These findings uncover an epigenetic reprogramming of the tumor-immune microenvironment, which fosters durable antitumor immunity and memory. Using in vivo models and human cancer datasets, Yang and colleagues identify a role for the epigenetic regulator Rnf2 in repressing the antitumor immune responses of natural killer and CD4(+) T cells.
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