Integrin-αV-mediated activation of TGF-β regulates anti-tumour CD8 T cell immunity and response to PD-1 blockade

Ines Malenica, Julien Adam, Stéphanie Corgnac, Laura Mezquita, Edouard Auclin, Isabelle Damei, Laetitia Grynszpan, Gwendoline Gros, Vincent de Montpréville, David Planchard, Nathalie Théret, Benjamin Besse, Fathia Mami-Chouaib

    Résultats de recherche: Contribution à un journalArticleRevue par des pairs

    37 Citations (Scopus)

    Résumé

    TGF-β is secreted in the tumour microenvironment in a latent, inactive form bound to latency associated protein and activated by the integrin αV subunit. The activation of latent TGF-β by cancer-cell-expressed αV re-shapes the tumour microenvironment, and this could affect patient responses to PD-1-targeting therapy. Here we show, using multiplex immunofluorescence staining in cohorts of anti-PD-1 and anti-PD-L1-treated lung cancer patients, that decreased expression of cancer cell αV is associated with improved immunotherapy-related, progression-free survival, as well as with an increased density of CD8+CD103+ tumour-infiltrating lymphocytes. Mechanistically, tumour αV regulates CD8 T cell recruitment, induces CD103 expression on activated CD8+ T cells and promotes their differentiation to granzyme B-producing CD103+CD69+ resident memory T cells via autocrine TGF-β signalling. Thus, our work provides the underlying principle of targeting cancer cell αV for more efficient PD-1 checkpoint blockade therapy.

    langue originaleAnglais
    Numéro d'article5209
    journalNature Communications
    Volume12
    Numéro de publication1
    Les DOIs
    étatPublié - 1 déc. 2021

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