ArticleCancer cell2019
An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.
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Article in Cancer cell, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 441 papers, 1 of them a synthesis that pooled it.
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441citing papers in PubMed, 1 pooled it
22.7field-weighted citation impact, top 1% of its field
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Who cites it
441 citing papers in PubMed, 1 synthesis or guideline pooled it, 618 citations in OpenAlex.
- Epigenetic regulation of major histocompatibility complexes in gastrointestinal malignancies and the potential for clinical interception.Clinical epigenetics · 2024Pooled it
- A Phase I/II Study of Valemetostat (DS-3201b), an EZH1/2 Inhibitor, in Combination with Irinotecan in Patients with Recurrent Small-Cell Lung Cancer.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Molecular classification and biomarkers of outcome with immunotherapy in extensive-stage small-cell lung cancer: analyses of the CASPIAN phase 3 study.Molecular cancer · 2024Trial
- Polycomb scaffolding subunit EED supports the SCLC neuroendocrine identity and EGFR-mutant LUAD-to-SCLC transformation.The Journal of clinical investigation · 2026Article
- Reframing cancer therapy through tumor plasticity.Nature cancer · 2026Review
- The immune phenotype of circulating tumor cells: from escape mechanisms to immunotherapy navigation.Biomarker research · 2026Review
- Resistance to PD-1/PD-L1 blockade: Mechanism and pharmacological strategies.Pharmacological research · 2026Review
- Cholangiocarcinoma:Unveiling the cold tumor microenvironment and strategies for immune rejuvenation.Oncogene · 2026Review
- DONSON links tumor-cell survival to MIF-associated macrophage remodeling in small cell lung cancer.Apoptosis : an international journal on programmed cell death · 2026Article
- Immune-pressure redistribution in resistance to PD-1/PD-L1 blockade: mechanisms, biomarkers, and therapeutic design.Molecular cancer · 2026Review
- Quantitative dissection of the metastatic cascade at single colony resolution.Research square · 2026Article
- Re-expression of MHC-I to treat CNS cancers.Oncotarget · 2026Review
- Therapy induced senescence promotes immunogenicity in acute myeloid Leukemia through reduced EZH2 activity.Nature communications · 2026Article
- XPO1-mediated TRIM21 nuclear export reprograms TREM2+ macrophage polarization by targeting IRF3 to augment anti-PD-1 efficacy in small cell lung cancer.Nature communications · 2026Article
- Long-term major histocompatibility complex class I suppression in astronauts and clinical implications.Communications biology · 2026Review
- Article
- EZH1/2 inhibition improves immunotherapy response through MHC Class II de-repression and neutrophil reprogramming.bioRxiv : the preprint server for biology · 2026Article
- Review
- Secreted luciferases as a minimally invasive 3R-compliant tool for accurate monitoring of tumor burden.Nature protocols · 2026Review
- The aryl hydrocarbon receptor inhibits antigen presentation to promote progression of pancreatic ductal adenocarcinoma.Journal of advanced research · 2026Article
381 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
28 authors at 6 institutions in 3 countries.
Marian L BurrPeter 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 SparbierPeter 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 ChanPeter 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 ChanPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
Ariena KersbergenACRF Cancer Biology and Stem Cell Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
Enid Y N LamPeter 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-YatesPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
Dane VassiliadisPeter 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 BellPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
Omer GilanPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
Susan JacksonPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
Lavinia TanPeter 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 WongPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
Sebastian HollizeckPeter 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 MichalakPeter 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 SiddleDepartment of Biological Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
Michael T McCabeEpigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA.
Rab K PrinjhaEpigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA; Epigenetics Research Unit, GlaxoSmithKline, Stevenage, UK.
Glen R GuerraPeter 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 SolomonPeter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia; Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, VIC 3052, Australia.
Shahneen SandhuPeter 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 DawsonPeter 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 BeavisPeter 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 TothillSir 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 CullinanePeter 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 LehnerCambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
Kate D SutherlandACRF 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 DawsonPeter 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.
The University of Melbourne · AUPeter MacCallum Cancer Centre · AUGlaxoSmithKline (United Kingdom) · GBGlaxoSmithKline (United States) · USUniversity of Southampton · GBWalter and Eliza Hall Institute of Medical Research · AU
Funding
Cancer Research UK 20097Wellcome Trust 210688/Z/18/Z
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.
Indexed as
AnimalsAntigen PresentationAntineoplastic Agents, ImmunologicalAntineoplastic Combined Chemotherapy ProtocolsCell Line, TumorDNA MethylationDown-RegulationDrug Resistance, NeoplasmEpigenetic RepressionFemaleGene Expression Regulation, NeoplasticHistocompatibility Antigens Class IHistone CodeHumansMiceMiddle AgedAntineoplastic Agents, ImmunologicalHistocompatibility Antigens Class IPolycomb Repressive Complex 2antigen presentationbivalencycancerepigenetic repressionEZH2histone methyltransferaseimmune evasionimmunotherapyMHC class Ipolycomb
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.