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

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State: Public
Version: Final published version
License: CC BY-NC 4.0
Serval ID
serval:BIB_7FDE10B2A046
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Tumor-specific cytolytic CD4 T cells mediate immunity against human cancer.
Journal
Science advances
Author(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
Publication state
Published
Issued date
02/2021
Peer-reviewed
Oui
Volume
7
Number
9
Pages
eabe3348
Language
english
Notes
Publication types: Journal Article
Publication Status: epublish
Abstract
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
Yes
Create date
01/03/2021 9:00
Last modification date
08/05/2021 6:32
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