Figure 1.

The interaction between CAFs and T cells in TME. CAFs have immunosuppressive roles by affecting Treg cells and cytotoxic CD8+ T cells. CAFs elicit the infiltration of Treg cells by secretion of CCL5 and CXCL12 and increase the proliferation of them through VEGF. In addition, CAFs facilitate the skewing of naïve CD4+ T cells to Treg cells. However, CAFs obstruct the migration of CD8+ T cells via various cytokines and chemokines such as CXCL12, VEGF, IL-6, and TGF-β. CAFs decrease the frequency and the activation of CD8+ T cells by PD-L1, PD-L2 and FASL. In addition, CAFs suppress an anti-tumor response of CD8+ T cells by upregulating PD-1 expression on the surface of T cells and by increasing PD-L1 expression on tumor through CXCL2. LRRC15+ CAFs induced by TGF-β signaling regulate anti-tumor response of CD8+ T cells. Furthermore, the accumulation of matrix protein, which is produced by CAFs can obstruct the migration of T cells and collagen can block the access of T cells to tumor, limiting the anti-tumor activity of T cells. Figure is generated with biorender (www.biorender.com).