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

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

Cancer cell (2019-10-01)

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

PMID31564637

ZUSAMMENFASSUNG

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.

MATERIALIEN

Produktnummer

Marke

Produktbeschreibung

CRISPR

Sigma-Aldrich

CRISPR/Cas9 Products and Services, Design and order CRISPR gRNA, Cas9, screening libraries, controls and companion products. Formats include plant, lentivirus, IVT-RNA, plasmid, synthetic, and protein.