Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy
| العنوان: | Eomes-Dependent Loss of the Co-activating Receptor CD226 Restrains CD8+ T Cell Anti-tumor Functions and Limits the Efficacy of Cancer Immunotherapy |
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| المؤلفون: | Stanislas Goriely, Marie-Véronique Joubert, Tobias Bald, Mark J. Smyth, Ludovic Martinet, Elena Morandi, Loïc Dupré, Laure Buisson, Nadège Carrié, Marianne Weulersse, Guillaume Gaud, Marie Le Moine, Thomas Gossye, Anne Dejean, Hervé Avet-Loiseau, Ashmitha Sundarrajan, Assia Asrir, Andrea C. Pichler, Michaël Pérès, Abdelhadi Saoudi, Alejandra Martinez, Julien Mazieres, Sahar Kassem, Elisa Brauns, Els Verhoeyen, Indrajit Das, Sabrina Maheo, Matthias Braun, Vera Pancaldi, Clara Maria Scarlata, Marine Cuisinier, Maha Ayyoub, Laura Do Souto, Lea Lemaitre, Arantxa Agesta, Camille Guillerey |
| المساهمون: | Centre de Recherches en Cancérologie de Toulouse (CRCT), Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), QIMR Berghofer Medical Research Institute, Institut Universitaire du Cancer de Toulouse - Oncopole (IUCT Oncopole - UMR 1037), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-CHU Toulouse [Toulouse]-Institut National de la Santé et de la Recherche Médicale (INSERM), Université libre de Bruxelles (ULB), Centre de Physiopathologie Toulouse Purpan (CPTP), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre International de Recherche en Infectiologie - UMR (CIRI), Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Ludwig Boltzmann Institute for Rare and Undiagnosed Diseases (LBI-RUD), Barcelona Supercomputing Center - Centro Nacional de Supercomputacion (BSC - CNS), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université de Toulouse (UT)-Université de Toulouse (UT)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Institut National de la Santé et de la Recherche Médicale (INSERM), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de Physiopathologie Toulouse Purpan ex IFR 30 et IFR 150 (CPTP) |
| المصدر: | Immunity, 53 (4 Immunity Immunity, Elsevier, 2020, 53 (4), pp.824-839.e10. ⟨10.1016/j.immuni.2020.09.006⟩ Immunity, 2020, 53 (4), pp.824-839.e10. ⟨10.1016/j.immuni.2020.09.006⟩ |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, MESH: Neoplasms / immunology, 8 Supplementary Figures, Lymphocyte, medicine.medical_treatment, [SDV]Life Sciences [q-bio], MESH: Programmed Cell Death 1 Receptor / immunology, CD226 (DNAM-1), MESH: Receptors, Antigen, T-Cell / immunology, MESH: Neoplasms / therapy, TCR signaling, 0302 clinical medicine, Cancer immunotherapy, MESH: Tumor Necrosis Factor Receptor Superfamily, Member 9 / immunology, Immunology and Allergy, Cytotoxic T cell, MESH: Animals, ComputingMilieux_MISCELLANEOUS, T cell exhaustion, MESH: Signal Transduction / immunology, MESH: CD8-Positive T-Lymphocytes / immunology, 3. Good health, Infectious Diseases, medicine.anatomical_structure, [SDV.IMM.IA]Life Sciences [q-bio]/Immunology/Adaptive immunology, 030220 oncology & carcinogenesis, Immunotherapy, MESH: Transcriptome / immunology, Immunology, Eomesodermin, 8 Figures, Biology, MESH: Antigens, Differentiation, T-Lymphocyte / immunology, Co-stimulation, 03 medical and health sciences, tumor immune escape, MESH: Mice, Inbred C57BL, MESH: Immune Checkpoint Inhibitors / immunology, medicine, MESH: Tumor Microenvironment / immunology, MESH: Mice, 96 References CD8 + T lymphocytes, Tumor microenvironment, MESH: Humans, immune checkpoint blockade, MESH: T-Box Domain Proteins / immunology, Immune checkpoint, MESH: Immunotherapy / methods, Sciences biomédicales, 030104 developmental biology, Cancer research, CD8 |
| الوصف: | Through complementary approaches, involving cancer patients’ samples and relevant mouse tumor models, Weulersse et al. reveal that CD8 T cells in the tumor microenvironment lose expression of the activating receptor CD226 (DNAM-1) in a manner that is Eomes dependent. CD226 loss restrains CD8 T cell function and limits the efficacy of cancer immunotherapy.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. CD226 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. |
| وصف الملف: | 1 full-text file(s): application/pdf |
| اللغة: | English |
| تدمد: | 1074-7613 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9dfe5be6f45852b02f2ba60ac27610fa http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/316003 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....9dfe5be6f45852b02f2ba60ac27610fa |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10747613 |
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