Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer.

Détails

Ressource 1Télécharger: eabe3348.full.pdf (6327.80 [Ko])
Etat: Public
Version: Final published version
Licence: CC BY-NC 4.0
ID Serval
serval:BIB_7FDE10B2A046
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer.
Périodique
Science advances
Auteur(s)
Cachot A., Bilous M., Liu Y.C., Li X., Saillard M., Cenerenti M., Rockinger G.A., Wyss T., Guillaume P., Schmidt J., Genolet R., Ercolano G., Protti M.P., Reith W., Ioannidou K., de Leval L., Trapani J.A., Coukos G., Harari A., Speiser D.E., Mathis A., Gfeller D., Altug H., Romero P., Jandus C.
ISSN
2375-2548 (Electronic)
ISSN-L
2375-2548
Statut éditorial
Publié
Date de publication
02/2021
Peer-reviewed
Oui
Volume
7
Numéro
9
Pages
eabe3348
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Résumé
CD4 T cells have been implicated in cancer immunity for their helper functions. Moreover, their direct cytotoxic potential has been shown in some patients with cancer. Here, by mining single-cell RNA-seq datasets, we identified CD4 T cell clusters displaying cytotoxic phenotypes in different human cancers, resembling CD8 T cell profiles. Using the peptide-MHCII-multimer technology, we confirmed ex vivo the presence of cytolytic tumor-specific CD4 T cells. We performed an integrated phenotypic and functional characterization of these cells, down to the single-cell level, through a high-throughput nanobiochip consisting of massive arrays of picowells and machine learning. We demonstrated a direct, contact-, and granzyme-dependent cytotoxic activity against tumors, with delayed kinetics compared to classical cytotoxic lymphocytes. Last, we found that this cytotoxic activity was in part dependent on SLAMF7. Agonistic engagement of SLAMF7 enhanced cytotoxicity of tumor-specific CD4 T cells, suggesting that targeting these cells might prove synergistic with other cancer immunotherapies.
Pubmed
Web of science
Open Access
Oui
Création de la notice
01/03/2021 8:00
Dernière modification de la notice
25/10/2021 17:50
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