Tumor-Derived Mesenchymal Stem Cells Use Distinct Mechanisms to Block the Activity of Natural Killer Cell Subsets.

Détails

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Etat: Public
Version: Final published version
ID Serval
serval:BIB_7586A39849E6
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Titre
Tumor-Derived Mesenchymal Stem Cells Use Distinct Mechanisms to Block the Activity of Natural Killer Cell Subsets.
Périodique
Cell reports
Auteur(s)
Galland S., Vuille J., Martin P., Letovanec I., Caignard A., Fregni G., Stamenkovic I.
ISSN
2211-1247 (Electronic)
Statut éditorial
Publié
Date de publication
19/09/2017
Peer-reviewed
Oui
Volume
20
Numéro
12
Pages
2891-2905
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: ppublish
Résumé
Mesenchymal stem cells (MSCs) display pleiotropic functions, which include secretion of soluble factors with immunosuppressive activity implicated in cancer progression. We compared the immunomodulatory effects on natural killer (NK) cells of paired intratumor (T)- and adjacent non-tumor tissue (N)-derived MSCs from patients with squamous cell lung carcinoma (SCC). We observed that T-MSCs were more strongly immunosuppressive than N-MSCs and affected both NK function and phenotype, as defined by CD56 expression. T-MSCs shifted NK cells toward the CD56 <sup>dim</sup> phenotype and differentially modulated CD56 <sup>bright/dim</sup> subset functions. Whereas MSCs affected both degranulation and activating receptor expression in the CD56 <sup>dim</sup> subset, they primarily inhibited interferon-γ production in the CD56 <sup>bright</sup> subset. Pharmacological inhibition of prostaglandin E2 (PGE2) synthesis and, in some MSCs, interleukin-6 (IL-6) activity restored NK function, whereas NK cell stimulation by PGE2 alone mimicked T-MSC-mediated immunosuppression. Our observations provide insight into how stromal responses to cancer dampen NK cell activity in human lung SCC.
Mots-clé
Aged, Aged, 80 and over, Carcinoma, Squamous Cell/pathology, Cell Separation, Coculture Techniques, Dinoprostone/metabolism, Down-Regulation, Female, Humans, Immunologic Factors/metabolism, Immunophenotyping, Immunosuppression, Interferon-gamma/metabolism, Interleukin-6/metabolism, Killer Cells, Natural/pathology, Lung Neoplasms/pathology, Lymphocytes, Tumor-Infiltrating/pathology, Male, Mesenchymal Stromal Cells/immunology, Mesenchymal Stromal Cells/metabolism, Middle Aged, Phenotype, Receptors, Immunologic/metabolism, Tumor Cells, Cultured, IL-6, PGE2, lung cancer, mesenchymal stem cells, natural killer cells
Pubmed
Web of science
Open Access
Oui
Création de la notice
25/09/2017 11:55
Dernière modification de la notice
20/08/2019 15:32
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