An evolutionarily conserved function of polycomb silences the MHC class I antigen presentation pathway and enables immune evasion in cancer
Details
Publication Year 2019-09-24, Volume 36, Issue #4, Page 385-401.e8
Journal Title
Cancer Cell
Publication Type
Journal Article
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.
Publisher
Cell Press
WEHI Research Division(s)
Cancer Biology And Stem Cells
PubMed ID
31564637
Open Access at Publisher's Site
https://doi.org/10.1016/j.ccell.2019.08.008
Rights Notice
Refer to copyright notice on published article.


Creation Date: 2019-10-23 02:22:50
Last Modified: 2019-10-23 02:31:55
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