GBM xenograft rejection in immunocompetent rats evidenced by MRI and immunohistology.
(A, top row) Serial MRI sections (from left to right) show a lesion that appeared ten weeks p.i. of low generation spheroids. The xenograft presented with a diffuse, weakly hyperintense signal on T2-weighted images without a clear demarcation toward the brain parenchyma (upper panel). Four weeks later, there is a reduction in the volume of the hyperintense area, and the lesion now shows a demarcated border toward the brain. Micrograph: Arrowheads point to perivascular (top) and peritumoral (bottom) leukocytic infiltrates in the brain. (B) Serial MRI slices representative of progressive tumor growth. The upper panel shows slices of the lesion fourteen weeks post implantation. The lower panel shows expansion of the tumor four weeks later. Control injections with PBS only did not produce any MRI signal apart from an outline of the needle track (hypo-intense) on early scans. Micrograph: No infiltration of leukocytes in the brain or around the tumor. Scale bars: 50 μm. C. Immunofluorescent micrographs show xenograft rejection (a to f) and tolerance (g, h). GBM cells are marked by human-specific nestin (red) and host cells by rat leukocytic common antigen (CD45, green). (a,b) Early phase of rejection. The tumor bed (T) is surrounded by a band of host leukocytes. CD45+ cells are observed in the meninges and perivascularly (arrowheads) in the brain. c.c.: corpus callosum. (c,d) Later stage of rejection. The tumor (asterisk) is infiltrated by host leukocytes. In the surrounding brain (B), numerous microvessels have perivascular cuffs indicating recruitment of leukocytes from the circulation (arrowheads). (e,f) Complete rejection. In the tumor bed, only islands of tumor cell foci remain (arrowheads). (g,h) Tolerance. A full-sized, vascularized tumor. Leukocytes are mainly seen around necrotic areas (N) and around tumor blood vessels. Infiltration into the tumor bed is limited. Original magnification of the figures; a, e, c, g: x50; b, d, h: x100, f: x200.