澳大利亚墨尔本大学的Mark A. Dawson和Marian L. Burr等研究人员合作发现，多梳蛋白的一种进化保守功能能够沉默MHC I类抗原呈递途径，使肿瘤免疫逃逸。相关论文2019年9月26日在线发表于《癌细胞》杂志。

研究人员发现，癌细胞中MHC I类（MHC-1）抗原呈递的缺失可引起免疫治疗抗性。全基因组CRISPR/Cas9筛选鉴定了多梳阻遏复合物2（PRC2）的进化保守功能，其介导MHC-1抗原加工途径（MHC-1 APP）的协调转录沉默，从而促进逃避T细胞介导的免疫。MHC-1低表达癌症中的MHC-1 APP基因启动子具有激活性的H3K4me3和抑制性的H3K27me3双重组蛋白修饰，从而沉默基础MHC-1表达并限制细胞因子诱导的上调。

MHC-1 APP基因上的双重修饰染色质是在胚胎干细胞中活跃的正常发育过程，在神经祖细胞分化过程中得以维持。这种生理性MHC-1沉默突显了一种保守的机制，即来源于这些原始组织的癌症利用PRC2活性来实现免疫逃逸。

附：英文原文

Title: An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer

Author: Marian L. Burr, Christina E. Sparbier, Kah Lok Chan, Yih-Chih Chan, Ariena Kersbergen, Enid Y.N. Lam, Elizabeth Azidis-Yates, Dane Vassiliadis, Charles C. Bell, Omer Gilan, Susan Jackson, Lavinia Tan, Stephen Q. Wong, Sebastian Hollizeck, Ewa M. Michalak, Hannah V. Siddle, Michael T. McCabe, Rab K. Prinjha, Glen R. Guerra, Benjamin J. Solomon, Shahneen Sandhu, Sarah-Jane Dawson, Paul A. Beavis, Richard W. Tothill, Carleen Cullinane, Paul J. Lehner, Kate D. Sutherland, Mark A. Dawson

Issue&Volume: 26 September 2019

Abstract:

Loss of MHC class I (MHC-I) antigen presentation in cancer cells can elicit immunotherapy resistance. A genome-wide CRISPR/Cas9 screen identified an evolutionarily conserved function of polycomb repressive complex 2 (PRC2) that mediates coordinated transcriptional silencing of the MHC-I antigen processing pathway (MHC-I APP), promoting evasion of T cell-mediated immunity. MHC-I APP gene promoters in MHC-I low cancers harbor bivalent activating H3K4me3 and repressive H3K27me3 histone modifications, silencing basal MHC-I expression and restricting cytokine-induced upregulation. Bivalent chromatin at MHC-I APP genes is a normal developmental process active in embryonic stem cells and maintained during neural progenitor differentiation. This physiological MHC-I silencing highlights a conserved mechanism by which cancers arising from these primitive tissues exploit PRC2 activity to enable immune evasion.

DOI: 10.1016/j.ccell.2019.08.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30376-9