Figure 4.

Tumor-associated dendritic cells in the tumor niche. Immature DCs and TAMs produce CCL18 in the tumor niche. This chemokine causes the chemotaxis and recruitment of immature DCs and naïve CD4⁺ T cells into the tumor niche. Next, CCL18 causes the differentiation of immature DCs into TADCs. The production of IL-10 increases in these cells, and thus the expression of IDO is autocrinally increased. However, PGE₂, produced by various cells (including TAMs and cancer cells), is also involved in this process. IDO is an enzyme that metabolizes tryptophan. The metabolites of this amino acid cause the differentiation of naïve CD4⁺ T cells into T_reg cells. In turn, T_reg cells produce IL-10, which enhances the functions of TADCs. In addition to their effects on T_reg cells, TADCs enhance tumor growth by producing HB-EGF and amphiregulin (activators of the EGFR receptors family).