TY - JOUR
T1 - RNF2 ablation reprograms the tumor-immune microenvironment and stimulates durable NK and CD4+ T-cell-dependent antitumor immunity
AU - Zhang, Zhuo
AU - Luo, Lin
AU - Xing, Chuan
AU - Chen, Yu
AU - Xu, Peng
AU - Li, Mao
AU - Zeng, Ling
AU - Li, Chao
AU - Ghosh, Sadashib
AU - Della Manna, Deborah
AU - Townes, Tim
AU - Britt, William J.
AU - Wajapeyee, Narendra
AU - Sleckman, Barry P.
AU - Chong, Zechen
AU - Leavenworth, Jianmei Wu
AU - Yang, Eddy S.
N1 - Publisher Copyright:
© 2021, The Author(s), under exclusive licence to Springer Nature America, Inc.
PY - 2021/10
Y1 - 2021/10
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=85117682903&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85117682903&partnerID=8YFLogxK
U2 - 10.1038/s43018-021-00263-z
DO - 10.1038/s43018-021-00263-z
M3 - Article
C2 - 35121884
AN - SCOPUS:85117682903
SN - 2662-1347
VL - 2
SP - 1018
EP - 1038
JO - Nature Cancer
JF - Nature Cancer
IS - 10
ER -