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Figure 1. Tumor necrosis factor receptor superfamily member 9 (TNFRSF9) is upregulated on tumor and endothelial cells in melanoma brain metastases. Immunohistochemistry revealing (a) strongly TNFRSF9-positive reactive astrocytes (gemistocytes; arrows) at the border between central nervous system tissue (black asterisk) and melanoma brain metastasis (blue asterisk). (b) Frequently, TNFRSF9 expression on melanoma cells increases (black arrows) with the distance from blood vessels (asterisks). (c) Smooth muscle cells of larger vessels (arrow) within melanoma brain metastasis (asterisk) exhibit strong TNFRSF9-positivity. (d) Apart from melanoma cells, TNFRSF9 is also upregulated on endothelial cells (arrows) of small intra-tumoral blood vessels. (e) Intra-tumoral lymphocytic infiltrates (green arrows) in melanoma brain metastasis (asterisk) also display membranous TNFRSF9-positivity. While some melanoma brain metastases showed strong TNFRSF9 expression (f) both at the cell membrane and within the cytoplasm, (g) others displayed only weak to moderate TNFRSF9 staining at the cell membrane (h: higher magnification of g. Black arrow: melanoma cells; green arrow: blood vessel). (Scale bars: a: 200 μm; b, c, d, f, g: 100 μm; e: 50 μm; h: 50 μm)