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Isolation and Flow Cytometric Analysis of Glioma-infiltrating Peripheral Blood Mononuclear Cells
Published on: November 28, 2015
Microglia limit brain tumor development by restricting tumor cell proliferation and inducing T-cell immunity
Tzu-Chieh Sun1,2, Ching-Fang Yu3,4,5, Sheng-Yan Wu1
1Department of Biomedical Engineering and Environmental Sciences, National Tsing-Hua University, Hsinchu, Taiwan.
Abstract:
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.
Insights
Tumor-associated microglia, unlike infiltrating macrophages, were found to restrict brain tumor growth. These microglia limit tumor cell proliferation and enhance anti-tumor immunity by increasing CD8 T cell infiltration.
Area of Science:
- Neuro-oncology
- Immunology
- Cell Biology
Background:
- Brain tumors contain diverse tumor-associated macrophages (TAMs), including microglia and infiltrating macrophages.
- The distinct roles of these macrophage populations in brain tumor progression remain unclear.
Purpose of the Study:
- To investigate the differential roles of tumor-associated microglia and infiltrating macrophages in brain tumor progression.
- To elucidate the mechanisms by which microglia influence tumor cell behavior and the anti-tumor immune response.
Main Methods:
- In vitro co-culture of astrocytoma cells (ALTS1C1) with microglial (BV2) or peripheral macrophage (RAW264.7) cell lines.
- In vivo studies involving co-inoculation of tumor cells and macrophages in mice.
- Immunohistochemical analysis of the tumor microenvironment (TME) and peripheral blood immune cell populations.
Main Results:
- Microglia (BV2), but not peripheral macrophages (RAW264.7), clustered astrocytoma cells (ALTS1C1), limiting tumor cell proliferation.
- Co-inoculation with microglia significantly prolonged survival in immune-competent mice, but not in immune-compromised mice.
- Microglia co-inoculation increased CD8 T cell infiltration, Granzyme B expression, and elevated CD8 T cells in peripheral blood while reducing myeloid-derived suppressor cells (MDSCs).
Conclusions:
- Tumor-associated microglia play a distinct role in restricting brain tumor development.
- Microglia limit tumor cell proliferation and promote T-cell-mediated anti-tumor immunity.
- Targeting microglia may represent a therapeutic strategy for brain tumors.
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