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

Animals Antigen Presentation / drug effects Antineoplastic Agents, Immunological / pharmacology Antineoplastic Combined Chemotherapy Protocols / pharmacology Cell Line, Tumor DNA Methylation / immunology Down-Regulation / drug effects Drug Resistance, Neoplasm / genetics Epigenetic Repression / drug effects Female Gene Expression Regulation, Neoplastic / drug effects Histocompatibility Antigens Class I / genetics Histone Code / drug effects Humans Mice Middle Aged Neoplasms / drug therapy Polycomb Repressive Complex 2 / antagonists & inhibitors T-Lymphocytes / immunology Tumor Escape / drug effects Xenograft Model Antitumor Assays
EZH2 MHC class I antigen presentation bivalency cancer epigenetic repression histone methyltransferase immune evasion immunotherapy polycomb

Journal

Cancer cell
ISSN: 1878-3686
Titre abrégé: Cancer Cell
Pays: United States
ID NLM: 101130617

Informations de publication

Date de publication:
14 10 2019
Historique:
received: 27 03 2019
revised: 26 06 2019
accepted: 24 08 2019
pubmed: 1 10 2019
medline: 26 5 2020
entrez: 1 10 2019
Statut: ppublish

Résumé

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.

Identifiants

DOI: 10.1016/j.ccell.2019.08.008 PMID: 31564637 PMC: PMC6876280
pubmed: 31564637
pii: S1535-6108(19)30376-9
doi: 10.1016/j.ccell.2019.08.008
pmc: PMC6876280
pii:
doi:

Substances chimiques

Antineoplastic Agents, Immunological 0
Histocompatibility Antigens Class I 0
Polycomb Repressive Complex 2 EC 2.1.1.43

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

385-401.e8

Subventions

Organisme : Wellcome Trust
ID : 210688/Z/18/Z
Pays : United Kingdom

Commentaires et corrections

Type : CommentIn
Type : CommentIn

Informations de copyright

Copyright © 2019 The Authors. Published by Elsevier Inc. All rights reserved.

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Auteurs

Marian L Burr (ML)

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. Electronic address: marian.burr@petermac.org.

Christina E Sparbier (CE)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Kah Lok Chan (KL)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Yih-Chih Chan (YC)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.

Ariena Kersbergen (A)

ACRF Cancer Biology and Stem Cell Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.

Enid Y N Lam (EYN)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Elizabeth Azidis-Yates (E)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.

Dane Vassiliadis (D)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Charles C Bell (CC)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Omer Gilan (O)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Susan Jackson (S)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.

Lavinia Tan (L)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Stephen Q Wong (SQ)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Sebastian Hollizeck (S)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Ewa M Michalak (EM)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Hannah V Siddle (HV)

Department of Biological Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.

Michael T McCabe (MT)

Epigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA.

Rab K Prinjha (RK)

Epigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA; Epigenetics Research Unit, GlaxoSmithKline, Stevenage, UK.

Glen R Guerra (GR)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Benjamin J Solomon (BJ)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Shahneen Sandhu (S)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Sarah-Jane Dawson (SJ)

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.

Paul A Beavis (PA)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Richard W Tothill (RW)

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.

Carleen Cullinane (C)

Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.

Paul J Lehner (PJ)

Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.

Kate D Sutherland (KD)

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.

Mark A Dawson (MA)

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. Electronic address: mark.dawson@petermac.org.

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Classifications MeSH

questionsmedicales.fr › Eucaryotes › Animaux › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes du système immunitaire › Immunité › Immunité acquise › Immunité cellulaire › Présentation d'antigène › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Actions chimiques et utilisations › Actions pharmacologiques › Utilisations thérapeutiques › Antinéoplasiques › Antinéoplasiques immunologiques › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Thérapeutique › Traitement médicamenteux › Association de médicaments › Protocoles de polychimiothérapie antinéoplasique › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Cellules › Cellules cultivées › Cellules cancéreuses en culture › Lignée cellulaire tumorale › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes génétiques › Méthylation de l'ADN › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Régulation négative › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes physiologiques › Phénomènes pharmacologiques et toxicologiques › Phénomènes pharmacologiques › Résistance aux substances › Résistance aux médicaments antinéoplasiques › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Épigenèse génétique › Répression épigénétique › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes génétiques › Régulation de l'expression des gènes › Régulation de l'expression des gènes tumoraux › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Facteurs biologiques › Antigènes › Isoantigènes › Antigènes d'histocompatibilité › Antigènes d'histocompatibilité de classe I › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes génétiques › Structures génétiques › Code histone › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Rodentia › Muridae › Murinae › Souris › An Evolutionarily Conserved Function of...
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questionsmedicales.fr › Tumeurs › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Facteurs de transcription › Protéines de répression › Protéines du groupe Polycomb › Complexe répresseur Polycomb-2 › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Systèmes sanguin et immunitaire › Système immunitaire › Leucocytes › Agranulocytes › Lymphocytes › Lymphocytes T › An Evolutionarily Conserved Function of...
questionsmedicales.fr › Phénomènes du système immunitaire › Échappement de la tumeur à la surveillance immunitaire › An Evolutionarily Conserved Function of...
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