Fig. 3.

The immunosuppressive effect of the tumor microenvironment. The hypoxia and acidosis of the tumor microenvironment (TME) contribute to immunosuppression via several mechanisms. These mechanisms include increased accumulation, activation, and expansion of immunosuppressive regulatory T (Treg) cells; recruitment of inflammatory monocytes and tumor-associated macrophages (TAMs) and reprogramming of TAMs towards the pro-tumor M₂ phenotype; suppression of dendritic cell (DC) maturation, which results in inhibiting activation of tumour-specific cytotoxic T lymphocytes (CTLs). Importantly, the programmed cell death protein 1 (PD-1)–programmed cell death 1 ligand 1 (PD-L1) pathway is often activated in the TME as a mechanism to evade anticancer immune responses, with up-regulation of PD-L1 expression on TAMs, DCs, and tumor cells. In addition, tumor-infiltrating CTLs typically up-regulate PD-1, limiting their cytotoxic potential against tumor cells. CCL20, C-C-motif chemokine ligand 20; CXCL, C-X-C-motif chemokine ligand; GM-CSF, granulocyte–macrophage colony-stimulating factor; TGFβ, transforming growth factor β; IL, Interleukin