| Literature DB >> 32027624 |
Jing Li1,2, Weichao Wang1,2, Yajia Zhang3, Marcin Cieślik3,4,5, Jipeng Guo1,2, Mengyao Tan3, Michael D Green1,2,6, Weimin Wang1,2, Heng Lin1,2, Wei Li1,2, Shuang Wei1,2, Jiajia Zhou1,2, Gaopeng Li1,2, Xiaojun Jing3, Linda Vatan1,2, Lili Zhao7, Benjamin Bitler8, Rugang Zhang8, Kathleen R Cho3,5, Yali Dou3,5, Ilona Kryczek1,2, Timothy A Chan9, David Huntsman10,11, Arul M Chinnaiyan3,6,12,13,14, Weiping Zou1,2,3,5,15.
Abstract
Whether mutations in cancer driver genes directly affect cancer immune phenotype and T cell immunity remains a standing question. ARID1A is a core member of the polymorphic BRG/BRM-associated factor chromatin remodeling complex. ARID1A mutations occur in human cancers and drive cancer development. Here, we studied the molecular, cellular, and clinical impact of ARID1A aberrations on cancer immunity. We demonstrated that ARID1A aberrations resulted in limited chromatin accessibility to IFN-responsive genes, impaired IFN gene expression, anemic T cell tumor infiltration, poor tumor immunity, and shortened host survival in many human cancer histologies and in murine cancer models. Impaired IFN signaling was associated with poor immunotherapy response. Mechanistically, ARID1A interacted with EZH2 via its carboxyl terminal and antagonized EZH2-mediated IFN responsiveness. Thus, the interaction between ARID1A and EZH2 defines cancer IFN responsiveness and immune evasion. Our work indicates that cancer epigenetic driver mutations can shape cancer immune phenotype and immunotherapy.Entities:
Keywords: Cancer immunotherapy; Immunology; T cells
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Year: 2020 PMID： 32027624 PMCID： PMC7190935 DOI： 10.1172/JCI134402
Source DB: PubMed Journal: J Clin Invest ISSN： 0021-9738 Impact factor: 14.808