Fig. 3
From: Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment
Macrophages interact with ECs or pericytes during tumour progression. TAM–EC interactions favour tumour angiogenesis: (1) TAMs secrete a multitude of cytokines or exosomes to activate ECs and enhance EC proliferation; (2) the ANG2-TIE2 axis is involved in angiogenesis by upregulating proangiogenic enzyme expression in TAMs. TAM–EC interactions in turn regulate TAM functions. ECs secrete CXCL2 to promote TAM recruitment. ANG2 from ECs also induces immunosuppressive TAMs in the TME. The TAM-EC crosstalk mediated by the DDL4:NOTCH2 ligand‒receptor interaction activates NOTCH signalling in TAMs, contributing to the formation of an immunosuppressive niche. Pericytes are involved in TAM recruitment and polarization via the production of MFG-E8 and CXCL14. TAMs induce pericyte migration and proangiogenic activity via PDGFB-PDGFRβ signalling