Cellular and molecular mechanism of blood monocyte-derived CD169+ macrophages enhancing antitumor immune responses against glioblastoma

Abstract

Therapies against glioblastoma multiforme (GBM) have been largely ineffective due to the infiltration of immunosuppressive tumor-associated macrophages (TAMs). Recent studies have demonstrated that TAMs can also be immune-activating. However, markers differentiating these heterogeneous macrophage populations have not been established. In this study, we identified a subset of macrophages expressing CD169 that promote an anti-tumoral microenvironment in GBM. Using single-cell transcriptome analyses, we found that CD169$^+$ macrophages in human and mouse gliomas produced proinflammatory chemokines and stimulated the accumulation of T cells and natural killer (NK) cells. Depletion of CD169$^+$ macrophages shortened the survival of mice with gliomas and reduced the cytotoxic functions of antitumor lymphocytes. We show that interferon gamma produced by NK cells was critical for the accumulation of CD169$^+$ macrophages in gliomas. Additionally, CD169 expression on macrophages increased the phagocytosis of apoptotic glioma cells. Our finding suggests that the CD169$^+$ subset of TAMs promotes antitumor immune responses against GBM.