Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation.

Détails

ID Serval
serval:BIB_4A546D8AF05A
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation.
Périodique
Cancer cell
Auteur⸱e⸱s
Duraiswamy J., Turrini R., Minasyan A., Barras D., Crespo I., Grimm A.J., Casado J., Genolet R., Benedetti F., Wicky A., Ioannidou K., Castro W., Neal C., Moriot A., Renaud-Tissot S., Anstett V., Fahr N., Tanyi J.L., Eiva M.A., Jacobson C.A., Montone K.T., Westergaard MCW, Svane I.M., Kandalaft L.E., Delorenzi M., Sorger P.K., Färkkilä A., Michielin O., Zoete V., Carmona S.J., Foukas P.G., Powell D.J., Rusakiewicz S., Doucey M.A., Dangaj Laniti D., Coukos G.
ISSN
1878-3686 (Electronic)
ISSN-L
1535-6108
Statut éditorial
Publié
Date de publication
13/12/2021
Peer-reviewed
Oui
Volume
39
Numéro
12
Pages
1623-1642.e20
Langue
anglais
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Résumé
The mechanisms regulating exhaustion of tumor-infiltrating lymphocytes (TIL) and responsiveness to PD-1 blockade remain partly unknown. In human ovarian cancer, we show that tumor-specific CD8 <sup>+</sup> TIL accumulate in tumor islets, where they engage antigen and upregulate PD-1, which restrains their functions. Intraepithelial PD-1 <sup>+</sup> CD8 <sup>+</sup> TIL can be, however, polyfunctional. PD-1 <sup>+</sup> TIL indeed exhibit a continuum of exhaustion states, with variable levels of CD28 costimulation, which is provided by antigen-presenting cells (APC) in intraepithelial tumor myeloid niches. CD28 costimulation is associated with improved effector fitness of exhausted CD8 <sup>+</sup> TIL and is required for their activation upon PD-1 blockade, which also requires tumor myeloid APC. Exhausted TIL lacking proper CD28 costimulation in situ fail to respond to PD-1 blockade, and their response may be rescued by local CTLA-4 blockade and tumor APC stimulation via CD40L.
Mots-clé
Antigen-Presenting Cells/metabolism, CD28 Antigens/metabolism, Humans, Immune Checkpoint Inhibitors/pharmacology, Immune Checkpoint Inhibitors/therapeutic use, Myeloid Cells/metabolism, Neoplasms/drug therapy, Neoplasms/immunology, Stem Cell Niche/genetics, CD28, CD40, CTLA-4, PD-1, TIL, dendritic cell, exhaustion, myeloid niche, ovarian, tumor
Pubmed
Web of science
Création de la notice
08/11/2021 11:25
Dernière modification de la notice
22/01/2022 7:32
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