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RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T-cell-dependent antitumor immunity.


ABSTRACT: 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.

SUBMITTER: Zhang Z 

PROVIDER: S-EPMC8809507 | biostudies-literature | 2021 Oct

REPOSITORIES: biostudies-literature

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RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4<sup>+</sup> T-cell-dependent antitumor immunity.

Zhang Zhuo Z   Luo Lin L   Xing Chuan C   Chen Yu Y   Xu Peng P   Li Mao M   Zeng Ling L   Li Chao C   Ghosh Sadashib S   Della Manna Deborah D   Townes Tim T   Britt William J WJ   Wajapeyee Narendra N   Sleckman Barry P BP   Chong Zechen Z   Leavenworth Jianmei Wu JW   Yang Eddy S ES  

Nature cancer 20211022 10


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  ...[more]

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