Tumor-associated macrophage (TAM) and myeloid-derived suppressor cell (MDSC) (TAM/MDSC)

Tumor-associated macrophages (TAMs) and myeloid-derived suppressor cells (MDSCs) are critical components of the tumor microenvironment (TME) that facilitate cancer progression by suppressing anti-tumor immunity (Mantovani et al., 2017). TAMs are typically polarized toward an M2-like phenotype, promoting angiogenesis, tissue remodeling, and the inhibition of cytotoxic T-cell activity through the secretion of cytokines like IL-10 and TGF-β (Cassetta & Pollard, 2018). MDSCs are a heterogeneous population of immature myeloid cells that expand during cancer and potently inhibit T-cell and natural killer cell functions via mechanisms involving arginase-1, iNOS, and reactive oxygen species (Gabrilovich, 2017). These cell populations represent significant hurdles for the efficacy of checkpoint inhibitors and other immunotherapies by maintaining an immunosuppressive niche (Kumar et al., 2016). Therapeutic strategies targeting TAMs and MDSCs focus on depleting these cells, blocking their recruitment from the bone marrow, or reprogramming them into pro-inflammatory, anti-tumor phenotypes (Kaneda et al., 2016). Drugs such as CSF1R inhibitors (e.g., pexidartinib) and PI3Kγ inhibitors (e.g., eganelisib) are currently being investigated to modulate these cells and enhance the overall immune response against tumors (Tap et al., 2015; Kaneda et al., 2016).

Other names

TAMsMDSCsM2-like macrophagesMonocytic MDSCs (M-MDSCs)Polymorphonuclear MDSCs (PMN-MDSCs)Suppressive myeloid cells

Therapeutic strategies involve the depletion of these cell populations, blockade of their recruitment to the tumor microenvironment via chemokine receptor inhibition, or functional reprogramming from an immunosuppressive (M2-like) to an immunostimulatory (M1-like) phenotype (Cassetta & Pollard, 2018; Kaneda et al., 2016).