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

当前位置： X-MOL 学术 › Cancer Cell › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.
Cancer Cell ( IF 48.8 ) Pub Date : 2019-09-26 , DOI: 10.1016/j.ccell.2019.08.008
Marian L Burr ₁ , Christina E Sparbier ₂ , Kah Lok Chan ₂ , Yih-Chih Chan ₃ , Ariena Kersbergen ₄ , Enid Y N Lam ₂ , Elizabeth Azidis-Yates ₃ , Dane Vassiliadis ₂ , Charles C Bell ₂ , Omer Gilan ₂ , Susan Jackson ₃ , Lavinia Tan ₂ , Stephen Q Wong ₂ , Sebastian Hollizeck ₂ , Ewa M Michalak ₂ , Hannah V Siddle ₅ , Michael T McCabe ₆ , Rab K Prinjha ₇ , Glen R Guerra ₂ , Benjamin J Solomon ₂ , Shahneen Sandhu ₂ , Sarah-Jane Dawson ₈ , Paul A Beavis ₂ , Richard W Tothill ₉ , Carleen Cullinane ₂ , Paul J Lehner ₁₀ , Kate D Sutherland ₁₁ , Mark A Dawson ₈

Affiliation

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia; Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
ACRF Cancer Biology and Stem Cell Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Department of Biological Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
Epigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA.
Epigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA; Epigenetics Research Unit, GlaxoSmithKline, Stevenage, UK.
Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia; Centre for Cancer Research, University of Melbourne, Parkville, Australia.
Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia; Centre for Cancer Research, University of Melbourne, Parkville, Australia; Department of Clinical Pathology, University of Melbourne, Melbourne, VIC, Australia.
Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
ACRF Cancer Biology and Stem Cell Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia; Department of Medical Biology, The University of Melbourne, Parkville, VIC 3010, Australia.

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.

中文翻译：

Polycomb 的进化保守功能可沉默 MHC I 类抗原呈递途径并实现癌症的免疫逃避。

癌细胞中 MHC I 类 (MHC-I) 抗原呈递的丧失会引发免疫治疗耐药性。全基因组 CRISPR/Cas9 筛选发现了多梳抑制复合物 2 (PRC2) 的进化保守功能，该功能介导 MHC-I 抗原加工途径 (MHC-I APP) 的协调转录沉默，促进 T 细胞介导的免疫的逃避。 MHC-I 低癌症中的 MHC-I APP 基因启动子含有二价激活 H3K4me3 和抑制性 H3K27me3 组蛋白修饰，沉默基础 MHC-I 表达并限制细胞因子诱导的上调。 MHC-I APP 基因的二价染色质是胚胎干细胞中活跃的正常发育过程，并在神经祖细胞分化过程中得以维持。这种生理性 MHC-I 沉默凸显了一种保守机制，这些原始组织产生的癌症利用 PRC2 活性来逃避免疫。

更新日期：2019-11-09

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11