FIGURE 2.

The influence of hypoxia and related metabolites on pDCs in HNSCC. A hypoxic TME promotes the recruitment of pDCs to tumor tissues via the upregulation of chemokines such as CXCR4 and CCL20 in a HIF‐1α‐dependent manner. The homing of pDCs to lymph nodes is also enhanced under hypoxic conditions due to upregulated CCR7. pDCs experience functional switching under hypoxic TME conditions. The maturation of pDCs is suppressed due to HIF‐1α‐mediated E2‐2 inhibition. Increased HMGB1 secretion by tumor cells inhibits the IFN‐α production of pDCs. Upregulated expression of IDO enhances pDC‐mediated induction of Tregs and hampers their antigen presentation ability