Fig. 3
From: Cancer-associated fibroblasts: an emerging target of anti-cancer immunotherapy
Immunosuppressive functions of different CAFs subtypes. Cancer-associated fibroblasts (CAFs) orchestrate an immunosuppressive tumor microenvironment. Different CAFs subtypes secrete numerous chemokines and cytokines, such as transforming growth factor-β (TGF-β), interleukin-6 (IL-6), interleukin-8 (IL-8), interleukin-13 (IL-13), CX-chemokine ligand 12 (CXCL12), CX-chemokine ligand 14 (CXCL14), and vascular endothelial growth factor A (VEGF), thereby inhibiting both the innate and adaptive anti-tumor immune response. Of note, some subpopulations express programmed cell death 1 ligand 1/2 (PD-L1/2), a target for immune checkpoint inhibitor. Metabolites or metabolic enzymes, such as indoleamine-2,3-dioxygenase (IDO), arginase (Arg), adenosine, and tryoptase produced by certain subtypes of CAFs favor the recruitment and differentiation of regulatory T cell (Tregs), mast cells, and tumor-associated macrophages (TAMs). Finally, CAFs can synthesize the extracellular matrix (ECM) components such as collagen, fibronectin, and matrix metalloproteinases (MMPs). Multiple CAF subtypes contribute to increased ECM stiffness, which in turn reduces the infiltration of effector T cells. MDSC myeloid-derived suppressor cell, DC dendritic cell, NK natural killer cells, TH cells CD4+ helper lymphocytes, N neutrophils, FAP fibroblast activation protein, PDPN podoplanin, CCL2 chemokine ligand 2, M-CSF macrophage colony-stimulating factor, PDGFR platelet-derived growth factor, APC antigen-processing cell, FASL FAS ligand