BioAcyl Corp

Fibroblast modification of the ECM regulates T‐cell entry into the lung in IAV infection and cancer. (A) Following IAV infection, ECM modified by fibroblast activity integrates innate immune signals to regulate the adaptive immune environment of the lung. Fibroblasts produce inflammatory chemokines and cytokines that drive ATII proliferation, for example interleukin‐1 beta (IL‐1β) and tumour necrosis factor‐alpha (TNF‐α). ECM protease‐producing fibroblasts degrade the ECM allowing T cells to migrate from the vasculature into the lung tissue to combat infection. Components are labelled with dotted line arrows. (B) Cancer‐associated fibroblasts (CAFs) also modify the ECM and regulate T‐cell entry into the tumour microenvironment. Inflammatory CAF (iCAF) subtypes secrete numerous chemokines and cytokines (indicated by curly arrows), such as transforming growth factor‐β (TGF‐β), interleukin‐6 (IL‐6), interleukin‐1 (IL‐1) and lymphocyte inhibitory factor (LIF) that promote the growth and proliferation of tumour cells. Other soluble factors released by iCAFs such as C‐X motif chemokine ligand 12 (CXCL12) and vascular endothelial growth factor A (VEGFA) inhibit (blunted arrow) the antitumour immune response via suppression of cytotoxic CD8 T cells. Finally, CAFs can synthesize ECM components (MMPs and collagens), and modification of the ECM by IL‐6 and C‐C motif chemokine ligand 2 (CCL2) contributes to increased ECM stiffness, which in turn reduces (blunted arrow) the infiltration of effector T cells to the tumour site. NSCLC, non‐small‐cell lung cancer.