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An Evolutionarily Conserved Function of Polycomb Silences the MHC Class I Antigen Presentation Pathway and Enables Immune Evasion in Cancer.
Burr, Marian L; Sparbier, Christina E; Chan, Kah Lok; Chan, Yih-Chih; Kersbergen, Ariena; Lam, Enid Y N; Azidis-Yates, Elizabeth; Vassiliadis, Dane; Bell, Charles C; Gilan, Omer; Jackson, Susan; Tan, Lavinia; Wong, Stephen Q; Hollizeck, Sebastian; Michalak, Ewa M; Siddle, Hannah V; McCabe, Michael T; Prinjha, Rab K; Guerra, Glen R; Solomon, Benjamin J; Sandhu, Shahneen; Dawson, Sarah-Jane; Beavis, Paul A; Tothill, Richard W; Cullinane, Carleen; Lehner, Paul J; Sutherland, Kate D; Dawson, Mark A.
Afiliación
  • 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
  • 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.
  • 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.
  • Chan YC; Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
  • Kersbergen A; ACRF Cancer Biology and Stem Cell Division, Walter and Eliza Hall Institute of Medical Research, Parkville, VIC 3052, Australia.
  • 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.
  • Azidis-Yates E; Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
  • 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.
  • 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.
  • 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.
  • Jackson S; Peter MacCallum Cancer Centre, 305 Grattan Street, Melbourne, VIC 3000, Australia.
  • 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.
  • 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.
  • 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.
  • 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.
  • Siddle HV; Department of Biological Sciences, University of Southampton, Southampton, UK; Institute for Life Sciences, University of Southampton, Southampton, UK.
  • McCabe MT; Epigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA.
  • Prinjha RK; Epigenetics Research Unit, Oncology R&D, GlaxoSmithKline, Collegeville, PA, USA; Epigenetics Research Unit, GlaxoSmithKline, Stevenage, UK.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • 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.
  • Lehner PJ; Cambridge Institute for Medical Research, Cambridge Biomedical Campus, Hills Road, Cambridge CB2 0XY, UK.
  • 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.
  • 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.
Cancer Cell ; 36(4): 385-401.e8, 2019 10 14.
Article en En | MEDLINE | ID: mdl-31564637
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.
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Protocolos de Quimioterapia Combinada Antineoplásica / Regulación Neoplásica de la Expresión Génica / Escape del Tumor / Complejo Represivo Polycomb 2 / Neoplasias Límite: Animals / Female / Humans / Middle aged Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article
Texto completo
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Texto completo: 1 Bases de datos: MEDLINE Asunto principal: Antígenos de Histocompatibilidad Clase I / Protocolos de Quimioterapia Combinada Antineoplásica / Regulación Neoplásica de la Expresión Génica / Escape del Tumor / Complejo Represivo Polycomb 2 / Neoplasias Límite: Animals / Female / Humans / Middle aged Idioma: En Revista: Cancer Cell Asunto de la revista: NEOPLASIAS Año: 2019 Tipo del documento: Article