Figure 3.

The tumor microenvironment influences cDC1 and natural killer (NK) cell phenotype and function. Immunosupressive factors like IL-10, TGF-β, and PGE2 can be secreted by tumor- and immune cells such as regulatory T cells (Tregs), tumor-associated macrophages (TAMs), or myeloid-derived-suppressor cells (MDSCs) present in the tumor microenvironment (TME). These factors, and hypoxia, can upregulate inhibitory receptors and decrease activating receptors on NK cells. Together with diminished IFN-γ secretion, the changed receptor expression results in reduced cytotoxicity of NK cells. Due to immunosuppressive factors in the TME cDC1s express low levels of XCR1 and CCR5 and display an immature phenotype with reduced CD80, CD86, and CD40 expression. Whereas checkpoint receptors and anti-inflammatory cytokine expression are upregulated.