Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2
| Autor: | Emilie Obre, Jean-François Moreau, Rodrigue Rossignol, Christelle Harly, Benoit Viollet, Angela Pappalardo, Vincent Pitard, Isabelle Soubeyran, Charlotte Domblides, Fiyaz Mohammed, Stéphane Claverol, Omar Hawchar, Sonia Netzer, Carla Cano, Layal Massara, Julie Déchanet-Merville, Carrie R. Willcox, Lydia Lartigue, Charlotte Mannat, S.P. Joyce, Benjamin Faustin, Isabelle Mahouche, Thomas Bachelet, Benjamin E. Willcox, Lionel Couzi |
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| Přispěvatelé: | Immunology from Concept and Experiments to Translation (ImmunoConcept), Université de Bordeaux (UB)-Centre National de la Recherche Scientifique (CNRS), University of Birmingham [Birmingham], TBM-Core [Bordeaux] (CNRS UMS 3427 - INSERM US 005), Université de Bordeaux (UB)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), CHU Bordeaux [Bordeaux], Centre Génomique Fonctionnelle Bordeaux [Bordeaux] (CGFB), Institut Polytechnique de Bordeaux-Université de Bordeaux Ségalen [Bordeaux 2], Cellomet [CHU Pellegrin, Bordeaux], CHU de Bordeaux Pellegrin [Bordeaux], Université de Bordeaux (UB), Actions for OnCogenesis understanding and Target Identification in ONcology (ACTION), Institut Bergonié [Bordeaux], UNICANCER-UNICANCER-Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), UNICANCER, ImCheck Therapeutics [Marseille], Laboratoire d'immunologie et d'immunogénétique [CHU Bordeaux], Laboratoire Maladies Rares: Génétique et Métabolisme (Bordeaux) (U1211 INSERM/MRGM), Université de Bordeaux (UB)-Groupe hospitalier Pellegrin-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Cochin (IC UM3 (UMR 8104 / U1016)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Paris Cité (UPCité), Université Paris Descartes - Paris 5 (UPD5), Janssen Research & Development, Bernardo, Elizabeth, Centre National de la Recherche Scientifique (CNRS)-Université de Bordeaux (UB), Flow Cytometry Facility / TransBioMed Core [Bordeaux] (INSERM US005 - CNRS UMS 3427 - UB), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Bordeaux Segalen - Bordeaux 2-Institut Bergonié [Bordeaux], UNICANCER-UNICANCER, Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université de Paris (UP) |
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
T cell CD3 Immunology [SDV.CAN]Life Sciences [q-bio]/Cancer Biology AMP-Activated Protein Kinases Cell Line 03 medical and health sciences 0302 clinical medicine [SDV.CAN] Life Sciences [q-bio]/Cancer Neoplasms medicine Ephrin Animals Humans Antigens Intraepithelial Lymphocytes Tissue homeostasis Mice Knockout Receptor EphA2 T-cell receptor AMPK Antibodies Monoclonal Receptors Antigen T-Cell gamma-delta General Medicine EPH receptor A2 Cell biology 030104 developmental biology medicine.anatomical_structure 030220 oncology & carcinogenesis Cancer cell biology.protein |
| Zdroj: | Science Immunology Science Immunology, 2021, 6 (61), pp.eaba9010. ⟨10.1126/sciimmunol.aba9010⟩ Science Immunology, American Association for the Advancement of Science, 2021, 6 (61), pp.eaba9010. ⟨10.1126/sciimmunol.aba9010⟩ |
| ISSN: | 2470-9468 |
| Popis: | International audience; Human γδ T cells contribute to tissue homeostasis and participate in epithelial stress surveillance through mechanisms that are not well understood. Here, we identified ephrin type-A receptor 2 (EphA2) as a stress antigen recognized by a human Vγ9Vδ1 TCR. EphA2 is recognized coordinately by ephrin A to enable γδ TCR activation. We identified a putative TCR binding site on the ligand-binding domain of EphA2 that was distinct from the ephrin A binding site. Expression of EphA2 was up-regulated upon AMP-activated protein kinase (AMPK)-dependent metabolic reprogramming of cancer cells, and coexpression of EphA2 and active AMPK in tumors was associated with higher CD3 T cell infiltration in human colorectal cancer tissue. These results highlight the potential of the human γδ TCR to cooperate with a co-receptor to recognize non-MHC-encoded proteins as signals of cellular dysregulation, potentially allowing γδ T cells to sense metabolic energy changes associated with either viral infection or cancer. |
| Databáze: | OpenAIRE |
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