Fig. 4

Multiple factors affect monocyte differentiation in the TME. High level of retinoic acid secreted by tumor cells can induce monocytes to differentiate into immunosuppressive macrophages by interfering with IRF4 and MAFB. Endogenous nucleoside adenosine induces abnormal development of DCs through A2B receptor, promoting activation of M2, synergistically enhancing immune escape. Similarly, other signaling molecules such as BMP4 and sap130 can also promote M2 polarization, and M2 secrete IL-10 to inhibit the secretion of IL-12 by vascular classic DCs (cDCs), thus inhibiting CD8⁺ T cell-dependent chemotherapy