Microglia limit brain tumor development by restricting tumor cell proliferation and inducing T-cell immunity

Tumor-associated macrophages (TAMs) in brain tumors contain two types of macrophages: tumor-associated microglia and infiltrating macrophages. This study explored whether these two populations have the same role in brain tumor progression. In an in vitro coculture model using the astrocytoma cells ALTS1C1 with either the microglial cell line BV2 or the peripheral macrophage cell line RAW264.7, only BV2, not RAW264.7, gathers ALTS1C1 into tumor cell clusters. These BV2-associated clusters limited ALTS1C1 proliferation but not BV2 cell growth. The in vivo studies show that the survival time of mice co-inoculated with ALTS1C1 and BV2 was prolonged from 30.4 ± 3.1 days to more than 77 days in immune-competent mice but not in immune-compromised mice. Examining the tumor microenvironment (TME) by immunohistochemical staining revealed that the co-inoculation of BV2 increased the CD8 T cells' infiltration and the expression of Granzyme B. Mice bearing with BV2-containing ALTS1C1 tumor exhibited a reduced level of circulating myeloid-derived suppressor cells (MDSCs) and an elevated level of CD8 T cells in peripheral blood compared to the ALTS1C1 tumor-bearing group. This study suggests tumor-associated microglia restrict brain tumor development by limiting tumor cell proliferation and inducing T-cell-associated antitumor immunity.