Inflammatory Cell Infiltrates Vary in Experimental Primary and Metastatic Brain Tumors

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Abstract
We have studied the cellular immune response that accompanies primary and metastatic brain cancers induced experimentally in rats by inoculation of RG-2 glioma and Walker 256 (W256) carcinoma cells, respectively. The inflammatory cell infiltrates were characterized with lectin histochemistry to visualize microglial cells and macrophages and with immunohistochemistry, using a panel of monoclonal antibodies, to detect major histocompatibility complex (MHC), lymphocytic, and macrophage antigens. The metastatic tumor was composed of a loose stroma with multiple, often large, necrotic areas, whereas the RG-2 glioma was composed of a dense collection of tumor cells showing only rare necrotic foci. Both tumor types were heavily infiltrated with microglia and/or macrophages, and these were positive for MHC Class II (Ia) antigens. Expression of MHC Class I antigens was absent from RG-2 glioma cells, but it was present in W256 metastatic carcinoma cells. The metastatic tumor was also characterized by a much heavier infiltrate of lymphocytes, as shown by the presence of cells positive for CD4, CD8, and leukocyte common antigens. These lymphocytic markers were absent from reactive microglia in the W256 carcinoma, whereas they were present in the RG-2 glioma. Polymorphonuclear leukocytes were seen only in the metastatic tumor. Our study delineates differences between the inflammatory cell infiltrates found in metastatic brain tumors and those found in primary brain tumors. The differences in cell composition and immunophenotype may indicate a more effective antitumor response in the metastatic tumor that could account for the observed tissue destruction.