Reactive tumor-associated macrophages and activated microglia (TAM/Microglia)

Reactive tumor-associated macrophages (TAMs) and activated microglia represent the predominant immune cell populations within the microenvironment of various tumors, particularly primary and metastatic brain cancers (PMID: 30305470). TAMs are derived from peripheral blood monocytes that infiltrate the tumor, while microglia are the resident immune cells of the central nervous system. In the context of malignancy, these cells often adopt a pro-tumorigenic (M2-like) phenotype, promoting immunosuppression, angiogenesis, and tumor invasion through the secretion of cytokines and growth factors (PMID: 24463430). Therapeutically, these cells are targeted via molecular pathways such as the CSF1/CSF1R axis to either deplete their numbers or repolarize them toward an anti-tumor (M1-like) state (PMID: 31015319). They also serve as critical indicators of neuroinflammation and disease progression in neurodegenerative conditions, often monitored via biomarkers like TSPO (PMID: 28232531). Drugs targeting these populations, such as pexidartinib, aim to disrupt the supportive niche they provide to cancer cells. However, targeting these cells presents challenges, including the risk of systemic immunosuppression and potential hepatotoxicity due to the depletion of resident tissue macrophages like Kupffer cells. Overall, modulating the activity of TAMs and microglia remains a key strategy in enhancing the efficacy of immunotherapy and treating CNS disorders.

Other names

TAMsTumor-associated macrophagesActivated microgliaM2-polarized macrophagesBrain-resident macrophagesGlioma-associated macrophages and microgliaGAMMs

Inhibition of CSF1R signaling to deplete or repolarize myeloid cells; Antagonism of CCR2 to prevent recruitment; Modulation of TREM2 signaling.