Fig. 2

Functional characterization of M1 and M2 macrophages. a Generally, M1 is tumor-resistant by directly lysing tumor cells after phagocytosis, and pro-inflammatory by enhanced tumor antigen-presenting ability or by indirectly promote the proliferation of immune cells like CD8 + T cells and NK cells (due to the effect of IL-6, IL-12 and TNF, et al.). b–d Whist and however, M2 is tumor-promoting through a repertoire of mechanisms, typically summarized as immunosuppression, tumor angiogenesis and neo-vascularization, and stromal activation and remodeling. b In contrast to M1-related immune response, M2 obstacles host immune states (Function 1). In tumor center (defined as Location 1) growth factors (including PDGF, TGFβ, HGF, and bFGF et al.) secreted by M2 would induce proliferation and metastasis of tumor cells. As a feed-back loop, cytokines and factors (including IL-4, IL-6, IL-10, MDF, TGF-β1 and PGE2 et al.) secreted by tumor cells enhance this effect in turn. c In avascular and peri-necrotic areas (defined as Location 2), HIF1α induced by hypoxia or low oxygen tension, in accordance with cytokines and factors (including VEGF, TNFα, IL-8 and bFGF et al.), and angiogenesis-modulating enzymes (including MMP and COX-2 et al.) would promote neo-vascularization and induce angiogenesis (Function 2). d In stromal areas (defined as Location 3), M2 actively impact on CAFs differentiation, BM breakdown, and collagen degradation and re-arrangement (Function 3). These combined stromal remodeling signatures would correspondingly induce tumor neo-vessels formation and maturation, as well as tumor invasion capability. The distinct tumor-related potentials of M1/M2 should be further investigated from known mechanisms illustrated in this figure