Cancer-associated fibroblasts drive CXCL13 production in activated T cells via TGF-beta

Introduction Tumour-reactive T cells producing the B-cell attractant chemokine CXCL13, in solid tumours, promote development of tertiary lymphoid structures (TLS) and are associated with improved prognosis responsiveness to checkpoint immunotherapy. Cancer fibroblasts dominant stromal cell type non-small lung cancer (NSCLC) where they co-localise can influence activation exhaustion. We questioned whether CAF directly CXCL13-production during activation. Methods characterised surface markers, cytokine production transcription factor expression CXCL13-producing NSCLC tumours paired non-cancerous samples using flow cytometry. then assessed human NSCLC-derived primary lines on from healthy donors patients vitro measuring CXCL13 cell-surface markers factors by Results CAFs significantly increased both CD4 + CD8 cells. CAF-induced lacked CXCR5 BCL6 displayed a peripheral helper phenotype. Furthermore, we demonstrate is induced TGF-β limited IL-2. provide reduce availability IL-2 (by reducing capacity for production) indirectly, expanding population activated Treg. Inhibition signalling prevented CAF-driven upregulation Treg expansion. Discussion Promoting represents newly described immune-regulatory function potential shape immune infiltrate tumour microenvironment altering effector-function infiltrating T-cells their attract B TLS formation.