Figure 2. The role of pDCs in the cancer microenvironment. (A) Peritumoral pDCs confer tumor promotion by immunosuppression. Tumors can inhibit the production of type I IFN from pDCs via secretion of TGF-β and TNF-α, which confer pDCs with an immunosuppressive capacity. The pDCs derived IL-6 induces MDSCs recruitment via CCL2 and MDSCs reinforce the tumor immunosuppressive microenvironment. The pDCs directly induce the generation of Treg by expression of IDO and ICOSL. Inversely, pDCs can inhibit anti-tumor effector CD4⁺ T cells and cytotoxic CD8⁺ T cells by expression of IDO or granzyme B. (B) The immunosuppressive tumor microenvironment supported by intratumoral pDCs can be reversed. In the presence of strong stimuli by microbial ligands such as CpG or viral RNA, pDCs can be activated to produce a large amount of type I IFN via TLR7 or TLR9 signaling. Type I IFN produced by pDCs can induce the maturation of immature immunosuppressive MDSCs into mature antigen-presenting cells, which then contribute to initiate anti-tumor immunity. Activated pDCs can exert direct cytotoxicity to tumor cells by expression of TNF-related apoptosis inducing ligand and granzyme B. Alternatively, activated pDCs stimulates NK cells to kill tumor cells. The pDCs can also act as an APC to prime anti-tumor T cells.

ICOSL, inducible costimulator ligand.