A Subset Of Monocyte-Derived Macrophages In Glioblastoma Multiforme Supports Antitumor Immune Responses.

Abstract Glioblastoma multiforme (GBM) is the most aggressive type of brain tumor and effective therapies are not well established. Lymphopenia and large infiltration of macrophages are major features of GBM. Although tumor-associated macrophages (TAMs) are known to suppress antitumor immune responses and support tumor growth and metastasis, recent studies reported that TAMs are a heterogeneous cell population, which includes both immune activating as well as immunosuppressive TAMs. However, because markers identifying these cells are not established, targeting TAMs is to induce antitumor immune responses is not yet an effective strategy. In this study, we identified a subset of macrophages that promote an anti-tumoral microenvironment in GBM. In single cell transcriptome analysis, we found that macrophages were divided to three populations based on their gene expression. One of these macrophage subsets expressed markers of monocyte-derived macrophages. These cells were a major source of pro-inflammatory chemokines among brain immune cells. In brain tumors without this monocyte-derived macrophage subpopulation, accumulation of CD4 and CD8 T cells and their cytokine production were diminished. Immuno-suppressive cells, such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs), and chemokines recruiting these cells were increased. Higher HIF-1α expression in tumors without these macrophages indicate that this subset might resolve hypoxia. Our finding suggests that this macrophage subset can support antitumor immune responses by suppressing a pro-tumoral microenvironment. Citation Format: Hyun-Jin Kim. A subset of monocyte-derived macrophages in glioblastoma multiforme supports antitumor immune responses [abstract]. In: Abstracts: AACR Virtual Special Conference: Tumor Immunology and Immunotherapy; 2020 Oct 19-20. Philadelphia (PA): AACR; Cancer Immunol Res 2021;9(2 Suppl):Abstract nr PO012.