细胞周期蛋白依赖激酶2
癌症研究
免疫系统
生物
免疫
免疫学
化学
作者
Yu Chen,Qiaomei Cai,Chaohu Pan,Wancheng Liu,Lili Li,Junxiao Liu,Meiling Gao,Xiaorong Li,Liguo Wang,Yu Rao,Heng Yang,Heng Yang
出处
期刊:Cancer immunology research
[American Association for Cancer Research]
日期:2022-02-18
卷期号:10 (4): 525-539
标识
DOI:10.1158/2326-6066.cir-21-0806
摘要
Abstract Inhibitors of cyclin-dependent kinase-2 (CDK2) are commonly used against several solid tumors, and their primary mechanisms of action were thought to include cell proliferation arrest, induction of cancer cell apoptosis and induction of differentiation. Here, we found that CDK2 inhibition by either small molecular inhibitors or genetic Cdk2 deficiency promoted antitumor immunity in murine models of fibrosarcoma and lung carcinoma. Mechanistically, CDK2 inhibition reduced phosphorylation of RB protein and transcription of E2F-mediated DNA methyltransferase 1 (DNMT1), which resulted in increased expression of endogenous retroviral RNA and type I IFN (IFN-I) response. The increased IFN-I response subsequently promoted antitumor immunity by enhancing tumor antigen presentation and CD8+ T-cell infiltration. Our studies provide evidence that inhibition of CDK2 in cancer cells suppresses tumor growth by enhancing antitumor immune responses in the tumor microenvironment, suggesting a new mechanism to enhance antitumor immunity by CDK2 inhibitors.
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