Site-specific immune response to implanted gliomas

Object. Immunotherapy for glioblastoma, has been uniformly ineffective. The immunological environment of the brain, with its low expression of major h istocompatibility complex (MHC) molecules and limited access for inflammato ry cells and humoral immune effectors due to the blood-brain barrier (BBB), may contribute to the failure of immunotherapy. The authors hypothesize th at brain tumors are protected from immune surveillance by an intact BBB at early stages of development. To investigate the immunological characteristi cs of early tumor growth, the authors compared the host response to a gliom a implanted into the brain and into subcutaneous tissue. Methods. Samples of tumors growing in the brain or subcutaneously in rats w ere obtained for 7 consecutive days and were examined immunohistochemically for MHC Class I & II molecules, and for CD4 and CD8 lymphocyte markers. Ad ditionally, B7-1 costimulatory molecule expression and lymphocyte-specific apoptosis were examined. Conclusions. On Days 3 and 4 after implantation, brain tumors displayed sig nificantly lower MHC Class ll expression and lymphocytic infiltration (p < 0.05). After Day 5, however, no differences were detected. The MHC Class II expressing cells within the brain tumors appeared to be infiltrating micro glia. Minimal B7-1 expression combined with lymphocyte-specific apoptosis w ere detected in both brain and subcutaneous tumors. Low MHC Class ll expres sion and low lymphocytic infiltration at early time points indicate the imp ortance of the immunologically privileged status of the brain during early tumor growth. These characteristics disappeared at later time points, possi bly because the increasing perturbation of the BBB alters the specific immu nological environment of the brain. The lack of B7-1 expression combined wi th lymphocyte apoptosis indicates clonal anergy of glioma-infiltrating lymp hocytes regardless of implantation site.