Robust ability of IFN-gamma to upregulate class II MHC antigen expression in tumor bearing rat brains.

T cells are attractive for delivering therapy to brain tumor, especially disseminated micro-tumor. However, to trigger effector function, tumor antigen must be re-presented to T cells, via major histocompatibility complex (MHC) proteins, at the tumor site. In normal brain, MHC+ antigen-presenting cells (APC) are rare, but abundant after gamma interferon (IFN-gamma) injection. Here we studied tumor-bearing brains. IFN-gamma (or buffer) was injected stereotactically into brains with established tumors from a panel of immunologically varied glioma cell lines, some expressing b-galactosidase as a micro-tumor marker. Four days later, cryostat sections were stained for tumor and MHC proteins. In phosphate-buffered saline-injected controls, class II MHC+ potential APC (microglia, macrophages) were seen only at (some) tumor sites. In rats that received IFN-gamma, class II+ potential APC were widespread, including all actual and potential micro-tumor sites and all tumor-free areas. In the same slides, neither class I nor class II MHC antigen was detected in neural cells or most tumor cells. This MHC pattern favors indirect re-presentation of tumor antigen, by tumor-adjacent APC. The robust response to IFN-gamma might also be exploited in other ways: activated microglia and macrophages can attack tumor directly, and class II+ APC may help mark micro-tumor sites.