Reactive tumor-associated macrophages and reactive microglia (TAMs/Microglia)

Reactive tumor-associated macrophages (TAMs) and reactive microglia are the primary immune components of the tumor microenvironment, particularly in central nervous system malignancies like glioblastoma. TAMs originate from bone marrow-derived monocytes that infiltrate the tissue, whereas microglia are the brain's resident myeloid cells; both become reactive in response to pathological stimuli (Quail & Joyce, 2017). In cancer, these cells are often subverted by the tumor to adopt an immunosuppressive, pro-angiogenic phenotype that facilitates tumor growth and resistance to therapy (Hambardzumyan et al., 2016). Targeting these populations is a major focus of current immunotherapy, utilizing strategies such as CSF1R inhibition to deplete the cells or repolarize them toward a tumor-clearing state (Butowski et al., 2016). Beyond oncology, reactive microglia are central to the pathogenesis of neurodegenerative diseases like Alzheimer's, where they contribute to chronic neuroinflammation and synaptic loss (Colonna & Butovsky, 2017).

Other names

Tumor-associated macrophagesTAMsReactive microgliaGlioma-associated macrophages and microgliaGAMsReactive myeloid cells

The primary mechanism of action for drugs targeting these populations is the inhibition of the Colony-Stimulating Factor 1 Receptor (CSF1R), which leads to the depletion of TAMs and microglia or their repolarization from a pro-tumorigenic (M2) to an anti-tumorigenic (M1) phenotype (Butowski et al., 2016). Other mechanisms include the blockade of the CD47-SIRPα don't eat me signaling pathway to enhance phagocytic activity and the antagonism of chemokine receptors like CCR2 to prevent the recruitment of peripheral monocytes into the tumor site (Quail & Joyce, 2017; Hambardzumyan et al., 2016).