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

Details

Serval ID
serval:BIB_4A546D8AF05A
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Myeloid antigen-presenting cell niches sustain antitumor T cells and license PD-1 blockade via CD28 costimulation.
Journal
Cancer cell
Author(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
Publication state
Published
Issued date
13/12/2021
Peer-reviewed
Oui
Volume
39
Number
12
Pages
1623-1642.e20
Language
english
Notes
Publication types: Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
Publication Status: ppublish
Abstract
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.
Keywords
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
Create date
08/11/2021 11:25
Last modification date
22/01/2022 7:32
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