Tmic-06. identity and gene profile of tumor-associated macrophages in glioblastoma

Glioblastoma (GBM) is the most aggressive and common type of brain tumor in adults, with patient survival times of approximately one year following diagnosis. The GBM microenvironment is composed of numerous non-neoplastic cells, including vascular endothelia, various infiltrating and resident immune cells, and non-neoplastic glial cells. The most abundant non-neoplastic cell population in the GBM microenvironment is tumor-associated macrophages (TAMs). TAMs comprise mixed populations of myeloid cells, including infiltrating macrophages from the blood circulation and resident brain microglia. TAMs are recruited to the GBM microenvironment, where they are hypothesized to perform immunosuppressive functions and release growth factors and cytokines in response to factors produced by neoplastic cells. In an effort to delineate the temporal and spatial dynamics of TAM composition during malignant gliomagenesis, we employed genetically-engineered mouse models of PDGF-driven GBM in combination with double-transgenic reporter mice that express GFP (green fluorescent protein) or RFP (red fluorescent protein) under the control of CX 3 CR1 or CCR2 promoters, respectively. Using this approach, we demonstrated that CX3CR1LoCCR2Hi monocytes are recruited to the GBM, where they transition in situ to CX3CR1HiCCR2Lo macrophages and CX3CR1HiCCR2- microglia-like cells. We found that infiltrating macrophages constitute ~80% of the total TAM population, with resident microglia accounting for th...
Source: Neuro-Oncology - Category: Cancer & Oncology Authors: Tags: TUMOR MICROENVIRONMENT Source Type: research