Subtypes ofmicroglia/macrophages relevant to the diagnosis and treatment of brain tumors

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Glioma-infiltrating microglia/macrophages are referred to as tumor-associated macrophages (TAMs). Transgenic (TG) rats expressingv-erbB, which is a viral form of the epidermal growth factor receptor, under transcriptional regulation by the S100-βpromoter develop brain tumors. We carried out immunohistochemical and morphometrical analyses of microglia/macrophages both in human gliomas and in the experimental tumors. Based onthe results, we found that the Iba1-positive, TAM with the morphology of activated/phagocytic cells were consistently found within glioma tissues. Iba1-positive TAMs of tumor core were significantly more activated than Iba1-positive microglia of non-neoplastic brain tissue in intraparenchymal, anaplastic oligodendrogliomas. In contrast to human gliomas, most TAMs in the experimental gliomas showed no or little expression against CD68, CD163, or CD204, although CD204-positive TAMs were observed in necrosis as well as in proliferating vascular wall. In conclusion, S-100β-v-erbB TG rats may serve as a useful animal model for further analysis of TAMs in terms of tumor cell proliferation, microvascular proliferation and phagocytosis, and as a tool for therapeutic use in malignant gliomas, although it should be noted that the polarization of TAMs towards the M2 phenotype remains unclear.