Tissue-resident and tumor-associated macrophages (TAM/TRM)

Tissue-resident macrophages (TRMs) are specialized, long-lived immune cells that reside in specific organs to maintain tissue homeostasis and provide immediate defense against pathogens (Ginhoux & Guilliams, 2016, Immunity). In the context of oncology, tumor-associated macrophages (TAMs) are a distinct or derived population that often dominates the leukocyte infiltrate within the tumor microenvironment. These cells frequently adopt an immunosuppressive 'M2-like' phenotype, which facilitates tumor progression by promoting angiogenesis, remodeling the extracellular matrix, and inhibiting the activity of cytotoxic T cells (Noy & Pollard, 2014, Immunity). Targeting TAMs has become a major focus in cancer immunotherapy, with strategies aiming to either deplete these cells, prevent their recruitment from the circulation, or reprogram them into 'M1-like' macrophages that can actively attack tumor cells. However, the high degree of plasticity and the overlap in markers between TAMs and healthy TRMs present significant challenges for achieving therapeutic selectivity and avoiding off-target toxicities. This entry is marked as incorrect because it describes a heterogeneous cell population rather than a single molecular target or receptor.

Other names

Tumor-associated macrophagesTissue-resident macrophagesTAMsTRMsM2-polarized macrophagesInfiltrating macrophagesMonocyte-derived macrophages

Therapeutic strategies targeting these cells include the depletion of macrophage populations via CSF1R inhibition, blockade of monocyte recruitment through the CCL2-CCR2 axis, and phenotypic reprogramming from an immunosuppressive M2-like state to a pro-inflammatory M1-like state to stimulate anti-tumor immunity (Cassetta & Pollard, 2018, Nat Rev Drug Discov). Additionally, 'don't eat me' signal inhibitors like CD47/SIRPα blockers enhance macrophage-mediated phagocytosis of malignant cells (Advani et al., 2018, NEJM).