Tumor-associated macrophage antigens (TAM antigens)

Tumor-associated macrophage antigens are a heterogeneous group of cell surface receptors and proteins expressed by macrophages within the tumor microenvironment. These antigens, such as Colony-stimulating factor 1 receptor (CSF1R), Mannose receptor C type 1 (CD206), and Scavenger receptor cysteine-rich type 1 protein M130 (CD163), typically identify the M2-polarized, immunosuppressive macrophage population (Mantovani et al., 2017, Nature Reviews Immunology). In the context of malignancy, these proteins facilitate tumor growth by promoting angiogenesis, suppressing T-cell activity, and aiding in the remodeling of the extracellular matrix. Therapeutic strategies targeting these antigens aim to reduce the density of tumor-associated macrophages (TAMs) or shift their functional state toward a pro-inflammatory M1 phenotype that supports anti-tumor immunity (Cannarile et al., 2017, Journal for ImmunoTherapy of Cancer). Drugs such as pexidartinib and various monoclonal antibodies are designed to block the signaling pathways or binding sites of these antigens to disrupt the pro-tumorigenic niche. While promising, targeting these antigens presents challenges due to their expression on essential resident macrophages in healthy tissues, potentially leading to systemic side effects like hepatotoxicity or periorbital edema (Tap et al., 2015, NEJM). Monitoring the expression of these antigens serves as a valuable biomarker for predicting patient response to immunotherapy and assessing the immune landscape of the tumor.

Other names

Tumor-associated macrophage-associated antigensTAM markersM2 macrophage antigensTumor-associated macrophage surface proteins

Targeting these antigens typically involves the depletion of tumor-associated macrophages, inhibition of their recruitment to the tumor microenvironment via the CSF1/CSF1R axis, or functional reprogramming from an immunosuppressive M2-like phenotype to a pro-inflammatory M1-like phenotype (Cannarile et al., 2017, Journal for ImmunoTherapy of Cancer).