Cancer cells impair monocyte-mediated T cell stimulation to evade immunity.

Détails

ID Serval
serval:BIB_6B66C99B58FA
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
Cancer cells impair monocyte-mediated T cell stimulation to evade immunity.
Périodique
Nature
Auteur⸱e⸱s
Elewaut A., Estivill G., Bayerl F., Castillon L., Novatchkova M., Pottendorfer E., Hoffmann-Haas L., Schönlein M., Nguyen T.V., Lauss M., Andreatta F., Vulin M., Krecioch I., Bayerl J., Pedde A.M., Fabre N., Holstein F., Cronin S.M., Rieser S., Laniti D.D., Barras D., Coukos G., Quek C., Bai X., Muñoz I Ordoño M., Wiesner T., Zuber J., Jönsson G., Böttcher J.P., Vanharanta S., Obenauf A.C.
ISSN
1476-4687 (Electronic)
ISSN-L
0028-0836
Statut éditorial
Publié
Date de publication
01/2025
Peer-reviewed
Oui
Volume
637
Numéro
8046
Pages
716-725
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
The tumour microenvironment is programmed by cancer cells and substantially influences anti-tumour immune responses <sup>1,2</sup> . Within the tumour microenvironment, CD8 <sup>+</sup> T cells undergo full effector differentiation and acquire cytotoxic anti-tumour functions in specialized niches <sup>3-7</sup> . Although interactions with type 1 conventional dendritic cells have been implicated in this process <sup>3-5,8-10</sup> , the underlying cellular players and molecular mechanisms remain incompletely understood. Here we show that inflammatory monocytes can adopt a pivotal role in intratumoral T cell stimulation. These cells express Cxcl9, Cxcl10 and Il15, but in contrast to type 1 conventional dendritic cells, which cross-present antigens, inflammatory monocytes obtain and present peptide-major histocompatibility complex class I complexes from tumour cells through 'cross-dressing'. Hyperactivation of MAPK signalling in cancer cells hampers this process by coordinately blunting the production of type I interferon (IFN-I) cytokines and inducing the secretion of prostaglandin E <sub>2</sub> (PGE <sub>2</sub> ), which impairs the inflammatory monocyte state and intratumoral T cell stimulation. Enhancing IFN-I cytokine production and blocking PGE <sub>2</sub> secretion restores this process and re-sensitizes tumours to T cell-mediated immunity. Together, our work uncovers a central role of inflammatory monocytes in intratumoral T cell stimulation, elucidates how oncogenic signalling disrupts T cell responses through counter-regulation of PGE <sub>2</sub> and IFN-I, and proposes rational combination therapies to enhance immunotherapies.
Mots-clé
Monocytes/immunology, Monocytes/metabolism, Mice, Dinoprostone/metabolism, Animals, Humans, Tumor Microenvironment/immunology, CD8-Positive T-Lymphocytes/immunology, CD8-Positive T-Lymphocytes/cytology, CD8-Positive T-Lymphocytes/metabolism, Female, Interferon Type I/metabolism, Interferon Type I/immunology, Dendritic Cells/immunology, Dendritic Cells/metabolism, Tumor Escape/immunology, Cell Line, Tumor, Lymphocyte Activation/immunology, Neoplasms/immunology, Neoplasms/pathology, Neoplasms/therapy, MAP Kinase Signaling System/immunology, Male, Cross-Priming/immunology, Antigen Presentation/immunology, Interleukin-15/metabolism, Interleukin-15/immunology, Mice, Inbred C57BL, Histocompatibility Antigens Class I/immunology, Histocompatibility Antigens Class I/metabolism, Chemokine CXCL9/metabolism
Pubmed
Web of science
Open Access
Oui
Création de la notice
02/12/2024 14:53
Dernière modification de la notice
18/01/2025 7:07
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