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

ABSTRACT: TGF-β is secreted in the tumour microenvironment in a latent, inactive form bound to latency associated protein and activated by the integrin α_V subunit. The activation of latent TGF-β by cancer-cell-expressed α_V 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 α_V is associated with improved immunotherapy-related, progression-free survival, as well as with an increased density of CD8⁺CD103⁺ tumour-infiltrating lymphocytes. Mechanistically, tumour α_V regulates CD8 T cell recruitment, induces CD103 express

SUBMITTER: Malenica I 

PROVIDER: S-EPMC8410945 | biostudies-literature | 2021 Sep

REPOSITORIES: biostudies-literature