Tumor-associated macrophage (TAM) (TAM)

Tumor-associated macrophages (TAMs) are a diverse population of myeloid cells residing within the tumor microenvironment that significantly influence cancer progression and therapeutic response (Mantovani et al., 2017). They are generally characterized by a functional plasticity that allows them to transition between a pro-inflammatory, anti-tumor M1 phenotype and an anti-inflammatory, pro-tumor M2 phenotype (Cassetta & Pollard, 2018). In most clinical cancers, TAMs predominantly exhibit M2-like characteristics, where they promote tumor growth by stimulating angiogenesis, remodeling the extracellular matrix, and suppressing adaptive immune responses (Vitale et al., 2019). Therapeutic strategies targeting TAMs aim to either deplete these cells, prevent their recruitment from the bone marrow, or reprogram them toward an M1-like state to restore anti-tumor immunity (Pathria et al., 2019). While targeting TAMs offers a potent strategy to overcome immunotherapy resistance, challenges remain regarding the heterogeneity of macrophage subsets and the risk of affecting homeostatic tissue-resident macrophages (Guerriero, 2018).

Other names

M1 macrophageM2 macrophageTumor-infiltrating macrophagePro-inflammatory macrophageAlternatively activated macrophage

Therapeutic strategies include the depletion of TAMs via CSF1R inhibition, the inhibition of macrophage recruitment through CCL2/CCR2 blockade, and the reprogramming of pro-tumor M2-like macrophages into anti-tumor M1-like macrophages using TLR agonists or CD40 antibodies. Additionally, blocking the CD47-SIRPα don't eat me signal enhances the phagocytic activity of TAMs against tumor cells (Cassetta & Pollard, 2018; Mantovani et al., 2017).