Suppressed Expression of T-Cell Costimulatory Molecules B7 and B70 in Human Glioblastomas In Vivo

The question of whether tumor cells can be recognized by the host immune system in an antigen-specific manner that is also major histocompatibility complex- (MHC-) restricted is a major issue in immunotherapy of glioblastomas. It was recently found that interaction of B7/B70 costimulatory molecules with their T-cell counterstructures CD28/CTLA-4 is essential for T-cell activation of both recognition phase and effector phase. To know whether proper T-cell activation can take place in glioblastomas in situ, we studied the expression of B7 (B7–1) and B70 (B7–2) molecules in vitro and in vivo. In vitro Northern blot analysis showed that five glioblastoma cell lines and six primary cultures did not express mRNA for B7 or B70 molecules. Cultured human fetal astrocytes either with or without interferon-y did not express the mRNA. Immunocytochemistry demonstrated that fetal astrocytes and glioblastoma cell lines are negative for B7 and B70 immunoreactive proteins. Inter-feron-γ increased HLA-DR (MHC class II) expression but did not induce B7/B70 molecules. In vivo, 21 glioblastoma tissues were studied with immunohistochemistry. Glioblastoma cells were found to be completely negative for both B7 and B70. At the tumor boundary or necrotic area, numerous macrophages (CD68+) were found positive for B7/B70. However, macrophages deep inside tumors almost invariably lacked B7/B70 expression. Northern blot analysis showed that 10 glioblastoma tissues did not express mRNA for B7/B70. The suppression of B7/B70 expression in both tumor cells and tumor-associated macrophages seems to be one mechanism of tumor evasion of host immune surveillance.