癌症研究
生物
免疫检查点
免疫系统
黑色素瘤
免疫
免疫疗法
免疫学
作者
Nivine Srour,Oscar D. Villarreal,Swanand Hardikar,Zhenbao Yu,Samuel E.J. Preston,Wilson H. Miller,Magdelena M. Szewczyk,Dalia Baršytė-Lovejoy,Xu Han,Taiping Chen,Sonia V. del Rincón,Stéphane Richard
出处
期刊:Cell Reports
[Elsevier]
日期:2022-03-01
卷期号:38 (13): 110582-110582
被引量:28
标识
DOI:10.1016/j.celrep.2022.110582
摘要
Despite the success of immune checkpoint inhibitor (ICI) therapy for cancer, resistance and relapse are frequent. Combination therapies are expected to enhance response rates and overcome this resistance. Herein, we report that combining PRMT7 inhibition with ICI therapy induces a strong anti-tumor T cell immunity and restrains tumor growth in vivo by increasing immune cell infiltration. PRMT7-deficient B16.F10 melanoma exhibits increased expression of genes in the interferon pathway, antigen presentation, and chemokine signaling. PRMT7 deficiency or inhibition with SGC3027 in B16.F10 melanoma results in reduced DNMT expression, loss of DNA methylation in the regulatory regions of endogenous retroviral elements (ERVs) causing their increased expression. PRMT7-deficient cells increase RIG-I and MDA5 expression with a reduction in the H4R3me2s repressive histone mark at their gene promoters. Our findings identify PRMT7 as a regulatory checkpoint for RIG-I, MDA5, and their ERV-double-stranded RNA (dsRNA) ligands, facilitating immune escape and anti-tumor T cell immunity to restrain tumor growth.
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