Fig. 2

The protumor activities of TAMs and TAM-targeted cancer therapies. a The protumor properties of TAMs. TAMs are commonly set in the protumor M2-like phenotype and have substantial influences on tumor initiation and progression. On the one hand, TAM-derived soluble molecules directly suppress the functions of tumor-infiltrating T cells and NK cells. Besides, autocrine IL-10 and TNF-α stimulate PD-L1 upregulation on TAMs. Also, TAMs directly suppress the antitumor immune response by recruiting Tregs and supporting their differentiation. On the other hand, TAMs also promote tumor progression in immune-independent ways, including tumor initiation and growth, angiogenesis, stemness, EMT, and distant metastasis. b TAM-targeted therapies. TAMs could be harnessed by targeting their recruitment, activation, immune checkpoint pathways, and metabolism. Besides, macrophage-based cell therapies, such as nanoparticle-loaded monocytes, CAR-M, and genetically engineered hematopoietic progenitors, also show potent antitumor activities. Abbreviations: TAM, tumor-associated macrophage; EMT, epithelial-mesenchymal transition; CSF1, colony-stimulating factor 1; CSF1R, CSF1 receptor; TLR, Toll-like receptor; STING, Stimulator of interferon genes; LILRB, Leukocyte immunoglobulin-like receptor B; SIRPα, Signal regulatory protein-α; IDO, Indoleamine 2,3-dioxygenase; CAR, Chimeric antigen receptor