Human γδ T cell sensing of AMPK-dependent metabolic tumor reprogramming through TCR recognition of EphA2.

Autor:	Harly C; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France., Joyce SP; Cancer Immunology and Immunotherapy Centre, Cancer Research UK Birmingham Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Domblides C; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France., Bachelet T; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France., Pitard V; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France.; Bordeaux University CNRS UMS3427, INSERM US05, Flow Cytometry Facility, TransBioMed Core, 33000 Bordeaux, France., Mannat C; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France., Pappalardo A; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France., Couzi L; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France.; Renal Transplantation Department, Bordeaux University Hospital, 33076 Bordeaux, France., Netzer S; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Massara L; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France.; Equipe Labellisée Ligue Contre le Cancer, Paris, France., Obre E; Cellomet, Centre de Génomique Fonctionnelle Bordeaux, University of Bordeaux, 33076 Bordeaux, France., Hawchar O; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France., Lartigue L; INSERM U1218 ACTION, Institut Bergonié, 229 cours de l'Argonne, 33076 Bordeaux Cedex, France., Claverol S; Centre de Génomique Fonctionnelle Bordeaux, University of Bordeaux, 33000 Bordeaux, France., Cano C; ImCheck Therapeutics, 13009 Marseille, France., Moreau JF; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France.; Immunology and Immunogenetics Laboratory, Bordeaux University Hospital, F-33000 Bordeaux, France., Mahouche I; INSERM, U1218 ACTION, F-33000 Bordeaux, France., Soubeyran I; INSERM, U1218 ACTION, F-33000 Bordeaux, France., Rossignol R; Cellomet, Centre de Génomique Fonctionnelle Bordeaux, University of Bordeaux, 33076 Bordeaux, France.; INSERM U1211, Rare diseases, Genetics and Metabolism, University of Bordeaux, Bordeaux, France., Viollet B; Institut Cochin, INSERM U1016, CNRS UMR 8104, Université Paris Descartes, Sorbonne Paris cité, Paris, France., Willcox CR; Cancer Immunology and Immunotherapy Centre, Cancer Research UK Birmingham Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Mohammed F; Cancer Immunology and Immunotherapy Centre, Cancer Research UK Birmingham Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK., Willcox BE; Cancer Immunology and Immunotherapy Centre, Cancer Research UK Birmingham Centre, Institute of Immunology and Immunotherapy, University of Birmingham, Birmingham B15 2TT, UK. jdechanet@immuconcept.org benfaustin@gmail.com b.willcox@bham.ac.uk., Faustin B; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France. jdechanet@immuconcept.org benfaustin@gmail.com b.willcox@bham.ac.uk.; Immunology Discovery, Janssen Research & Development, San Diego, CA, USA., Déchanet-Merville J; Bordeaux University, CNRS, ImmunoConcept, UMR 5164, 33000 Bordeaux, France. jdechanet@immuconcept.org benfaustin@gmail.com b.willcox@bham.ac.uk.; Equipe Labellisée Ligue Contre le Cancer, Paris, France.; Bordeaux University CNRS UMS3427, INSERM US05, Flow Cytometry Facility, TransBioMed Core, 33000 Bordeaux, France.
Jazyk:	angličtina
Zdroj:	Science immunology [Sci Immunol] 2021 Jul 30; Vol. 6 (61).
DOI:	10.1126/sciimmunol.aba9010
Abstrakt:	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. (Copyright © 2021 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
Databáze:	MEDLINE
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