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.
Dutta
Tanya
T
CNS & Brain Tumor Immunology Laboratory, Department of Neurosurgery, Brigham and Women's Hospital and Harvard Medical School, Boston, MA, USA.
Spence
Alexander
A
Lampson
Lois A
LA
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D000949:Histocompatibility Antigens Class II / Q000378:metabolism*; D021621:Imaging, Three-Dimensional; D007267:Injections; D007371:Interferon-gamma / Q000008:administration & dosage / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011919:Rats, Inbred Strains; D015854:Up-Regulation
D000949:Histocompatibility Antigens Class II; D007371:Interferon-gamma