Tumor-associated macrophages (TAMs) are a class of immune cells present in high numbers in the microenvironment of solid tumors.
[1] The composition of monocyte-derived macrophages and tissue-resident macrophages in the tumor microenvironment depends on the tumor type, stage, size, and location, thus it has been proposed that TAM identity and heterogeneity is the outcome of interactions between tumor-derived, tissue-specific, and developmental signals.
The formation of vasculature also facilitates the escape of malignant cells into blood circulation and the onset of metastasis.
[8] Tie2+ TAMs associate with blood vessels through angiopoietin-2 produced by endothelial cells and activate angiogenesis through paracrine signaling.
[10][11] In low-oxygen regions of a solid tumor, mononuclear myeloid-derived suppressor cells (M-MDSC) quickly turn into tumor-associated macrophages.
[19] Recently, Siglec-15 has also been identified as an immune suppressive molecule that is solely expressed on TAMs, and could be a potential therapeutic target for cancer immunotherapy.
More comprehensive classification systems that account for the dynamic nature of macrophages have been proposed,[2] but have not been adopted by the immunological research community.
[26][27][28][29] CSF1R inhibitors such as PLX3397 have also been shown to alter the distribution of TAMs throughout the tumor and promote enrichment of the classically activated M1-like phenotype.
[32] Re-polarization of TAMs from a M2 to M1 phenotype by drug treatments has shown the ability to control tumor growth,[33][17] including in combination with checkpoint inhibitor therapy.