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Glioblastomas acquire myeloid-affiliated transcriptional programs via epigenetic immunoediting to elicit immune evasion.
Gangoso, Ester; Southgate, Benjamin; Bradley, Leanne; Rus, Stefanie; Galvez-Cancino, Felipe; McGivern, Niamh; Güç, Esra; Kapourani, Chantriolnt-Andreas; Byron, Adam; Ferguson, Kirsty M; Alfazema, Neza; Morrison, Gillian; Grant, Vivien; Blin, Carla; Sou, IengFong; Marques-Torrejon, Maria Angeles; Conde, Lucia; Parrinello, Simona; Herrero, Javier; Beck, Stephan; Brandner, Sebastian; Brennan, Paul M; Bertone, Paul; Pollard, Jeffrey W; Quezada, Sergio A; Sproul, Duncan; Frame, Margaret C; Serrels, Alan; Pollard, Steven M.
Afiliação
  • Gangoso E; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Southgate B; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Bradley L; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Rus S; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Galvez-Cancino F; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK.
  • McGivern N; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Güç E; Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, Edinburgh Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Kapourani CA; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Byron A; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Ferguson KM; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Alfazema N; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Morrison G; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Grant V; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Blin C; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Sou I; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Marques-Torrejon MA; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Conde L; Bill Lyons Informatics Centre, Department of Cancer Biology, University College London Cancer Institute, London WC1E 6BT.
  • Parrinello S; Samantha Dickson Brain Cancer Unit, Department of Cancer Biology, University College London Cancer Institute, London WC1E 6BT, UK.
  • Herrero J; Bill Lyons Informatics Centre, Department of Cancer Biology, University College London Cancer Institute, London WC1E 6BT.
  • Beck S; Medical Genomics Research Group, Department of Cancer Biology, University College London Cancer Institute, London, WC1E 6BT.
  • Brandner S; Division of Neuropathology and Department of Neurodegenerative Disease, UCL Queen Square Institute of Neurology, UCL, London, UK.
  • Brennan PM; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Bertone P; Department of Medicine, Alpert Medical School, Brown University, Providence, RI 02903, USA.
  • Pollard JW; Centre for Reproductive Health, The University of Edinburgh, The Queen's Medical Research Institute, Edinburgh Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Quezada SA; Cancer Immunology Unit, Research Department of Haematology, University College London Cancer Institute, London WC1E 6BT, UK.
  • Sproul D; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Frame MC; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK.
  • Serrels A; Centre for Inflammation Research, The University of Edinburgh, The Queen's Medical Research Institute, Edinburgh Little France Crescent, Edinburgh EH16 4TJ, UK.
  • Pollard SM; Centre for Regenerative Medicine, Institute for Regeneration and Repair, University of Edinburgh, 5 Little France Drive, Edinburgh EH16 4UU, UK; CRUK Edinburgh Centre, Institute of Genetics and Molecular Medicine, Crewe Road South, University of Edinburgh, Edinburgh EH42XR, UK. Electronic address: s
Cell ; 184(9): 2454-2470.e26, 2021 04 29.
Article em En | MEDLINE | ID: mdl-33857425
Glioblastoma multiforme (GBM) is an aggressive brain tumor for which current immunotherapy approaches have been unsuccessful. Here, we explore the mechanisms underlying immune evasion in GBM. By serially transplanting GBM stem cells (GSCs) into immunocompetent hosts, we uncover an acquired capability of GSCs to escape immune clearance by establishing an enhanced immunosuppressive tumor microenvironment. Mechanistically, this is not elicited via genetic selection of tumor subclones, but through an epigenetic immunoediting process wherein stable transcriptional and epigenetic changes in GSCs are enforced following immune attack. These changes launch a myeloid-affiliated transcriptional program, which leads to increased recruitment of tumor-associated macrophages. Furthermore, we identify similar epigenetic and transcriptional signatures in human mesenchymal subtype GSCs. We conclude that epigenetic immunoediting may drive an acquired immune evasion program in the most aggressive mesenchymal GBM subtype by reshaping the tumor immune microenvironment.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Neoplasias Encefálicas / Glioblastoma / Células Mieloides / Epigênese Genética / Evasão da Resposta Imune / Microambiente Tumoral Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Células-Tronco Neoplásicas / Neoplasias Encefálicas / Glioblastoma / Células Mieloides / Epigênese Genética / Evasão da Resposta Imune / Microambiente Tumoral Limite: Animals / Humans / Male Idioma: En Ano de publicação: 2021 Tipo de documento: Article