Disease-associated microglia adopt stage-specific phenotypes that regulate T cell fate and immunity in glioma

Glioma microenvironment contains numerous myeloid cells, including brain-resident microglia and recruited monocytes and macrophages (Mo/Mφ). Previous researches studied these cells collectively and revealed their pro-tumor effects. Yet, little is known about the differences among these myeloid populations. Here we revealed the phenotypic characteristics, spatial variances, and dynamic changes of these relatively heterogeneous cell populations by single-cell sequencing analysis. Microglia were pro-inflammatory transiently, and soon skewed to restore the homeostasis of the central nervous system (CNS). Notably, a subset of glioma-associated microglia shared similar trait in a diverse spectrum of neuropathogenesis. Mo/Mφ, on the other hand, were responsible for various tumor-promoting effects, such as angiogenesis, tumor invasion, and immune evasion. Moreover, the Mo/Mφ subsets presented prognostic and classificatory value in clinical application. Conclusively, these results eliminate the long-existing ambiguity about the role of microglia and Mo/Mφ in glioma pathogenesis, and reveal their prognostic and therapeutic value for glioma patients.