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Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy.
Weulersse, Marianne; Asrir, Assia; Pichler, Andrea C; Lemaitre, Lea; Braun, Matthias; Carrié, Nadège; Joubert, Marie-Véronique; Le Moine, Marie; Do Souto, Laura; Gaud, Guillaume; Das, Indrajit; Brauns, Elisa; Scarlata, Clara M; Morandi, Elena; Sundarrajan, Ashmitha; Cuisinier, Marine; Buisson, Laure; Maheo, Sabrina; Kassem, Sahar; Agesta, Arantxa; Pérès, Michaël; Verhoeyen, Els; Martinez, Alejandra; Mazieres, Julien; Dupré, Loïc; Gossye, Thomas; Pancaldi, Vera; Guillerey, Camille; Ayyoub, Maha; Dejean, Anne S; Saoudi, Abdelhadi; Goriely, Stanislas; Avet-Loiseau, Hervé; Bald, Tobias; Smyth, Mark J; Martinet, Ludovic.
Afiliación
  • Weulersse M; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Asrir A; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Pichler AC; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Lemaitre L; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Braun M; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Carrié N; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Joubert MV; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Le Moine M; UCR-I (ULB Centre for Research in Immunology), Université Libre de Bruxelles, Institute for Medical Immunology (IMI), Gosselies, 6041 Belgium.
  • Do Souto L; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Gaud G; Centre de physiopathologie de Toulouse Purpan (CPTP), INSERM UMR 1043, CNRS UMR 5282, UPS, Toulouse, France.
  • Das I; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Brauns E; UCR-I (ULB Centre for Research in Immunology), Université Libre de Bruxelles, Institute for Medical Immunology (IMI), Gosselies, 6041 Belgium.
  • Scarlata CM; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Morandi E; Centre de physiopathologie de Toulouse Purpan (CPTP), INSERM UMR 1043, CNRS UMR 5282, UPS, Toulouse, France.
  • Sundarrajan A; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Cuisinier M; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Buisson L; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Maheo S; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Kassem S; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Agesta A; Centre de physiopathologie de Toulouse Purpan (CPTP), INSERM UMR 1043, CNRS UMR 5282, UPS, Toulouse, France.
  • Pérès M; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Verhoeyen E; Université Côte d'Azur, INSERM, C3M, Nice, France; Centre international de recherche en infectiologie (CIRI), Inserm U1111, CNRS UMR5308, Ecole Normale Supérieure de Lyon, Université Claude Bernard Lyon 1, Lyon, France.
  • Martinez A; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Mazieres J; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Dupré L; Centre de physiopathologie de Toulouse Purpan (CPTP), INSERM UMR 1043, CNRS UMR 5282, UPS, Toulouse, France; Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Vienna, Austria.
  • Gossye T; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France.
  • Pancaldi V; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Barcelona Supercomputing Center, Barcelona, Spain.
  • Guillerey C; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Ayyoub M; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Dejean AS; Centre de physiopathologie de Toulouse Purpan (CPTP), INSERM UMR 1043, CNRS UMR 5282, UPS, Toulouse, France.
  • Saoudi A; Centre de physiopathologie de Toulouse Purpan (CPTP), INSERM UMR 1043, CNRS UMR 5282, UPS, Toulouse, France.
  • Goriely S; UCR-I (ULB Centre for Research in Immunology), Université Libre de Bruxelles, Institute for Medical Immunology (IMI), Gosselies, 6041 Belgium.
  • Avet-Loiseau H; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France.
  • Bald T; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Smyth MJ; QIMR Berghofer Medical Research Institute, Herston, Queensland, Australia.
  • Martinet L; Cancer Research Center of Toulouse (CRCT), Institut National de la Santé et de la Recherche Médicale (INSERM) UMR 1037, Centre National de la Recherche Scientifique (CNRS), Université Paul Sabatier (UPS), Toulouse, France; Institut Universitaire du Cancer, CHU Toulouse, France. Electronic address: l
Immunity ; 53(4): 824-839.e10, 2020 10 13.
Article en En | MEDLINE | ID: mdl-33053331
CD8+ T cells within the tumor microenvironment (TME) are exposed to various signals that ultimately determine functional outcomes. Here, we examined the role of the co-activating receptor CD226 (DNAM-1) in CD8+ T cell function. The absence of CD226 expression identified a subset of dysfunctional CD8+ T cells present in peripheral blood of healthy individuals. These cells exhibited reduced LFA-1 activation, altered TCR signaling, and a distinct transcriptomic program upon stimulation. CD226neg CD8+ T cells accumulated in human and mouse tumors of diverse origin through an antigen-specific mechanism involving the transcriptional regulator Eomesodermin (Eomes). Despite similar expression of co-inhibitory receptors, CD8+ tumor-infiltrating lymphocyte failed to respond to anti-PD-1 in the absence of CD226. Immune checkpoint blockade efficacy was hampered in Cd226-/- mice. Anti-CD137 (4-1BB) agonists also stimulated Eomes-dependent CD226 loss that limited the anti-tumor efficacy of this treatment. Thus, CD226 loss restrains CD8+ T cell function and limits the efficacy of cancer immunotherapy.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Diferenciación de Linfocitos T / Linfocitos T CD8-positivos / Proteínas de Dominio T Box / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Antígenos de Diferenciación de Linfocitos T / Linfocitos T CD8-positivos / Proteínas de Dominio T Box / Neoplasias Tipo de estudio: Prognostic_studies Límite: Animals / Humans Idioma: En Revista: Immunity Asunto de la revista: ALERGIA E IMUNOLOGIA Año: 2020 Tipo del documento: Article País de afiliación: Francia Pais de publicación: Estados Unidos