Expression of Fas ligand by microglia: possible role in glioma immune evasion.
The immune-privileged status of the central nervous system is thought to limit the application of immunotherapy for treatment of malignant brain tumors. Because the Fas pathway has been proposed to play a role in immune evasion, we examined the effect of tumor environment on the expression of Fas ligand (FasL) in a mouse glioma model. Immunoblotting revealed the expression of membrane-bound FasL to nearly double when murine G26 gliomas were propagated intracranially (IC) as compared to subcutaneously (SC). Further analysis by flow cytometry revealed microglia, which were absent in the SC tumors, to account for half of the FasL expression in the IC tumors. Interestingly, when FasL activity was inhibited in IC tumors, the proportion of tumor-infiltrating leukocytes increased three-fold, reaching the same frequency as the SC tumors. These observations suggest that microglia are a major source of FasL expression in brain tumors and possibly contribute to the local immunosuppressive milieu of malignant gliomas.
Badie
B
B
Neuro-oncology Laboratory, Department of Neurological Surgery, University of Wisconsin School of Medicine, K3/805 Clinical Science Center, 600 Highland Ave., Madison, WI 53792-3232, USA. badie@neurosurg.wisc.edu
Schartner
J
J
Prabakaran
S
S
Paul
J
J
Vorpahl
J
J
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D000954:Antigens, Surface / Q000276:immunology; D001812:Blood-Brain Barrier / Q000276:immunology; D001932:Brain Neoplasms / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D002465:Cell Movement / Q000276:immunology; D019008:Drug Resistance, Neoplasm / Q000276:immunology*; D053222:Fas Ligand Protein; D005434:Flow Cytometry; D005625:Frontal Lobe / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D005910:Glioma / Q000188:drug therapy / Q000276:immunology* / Q000378:metabolism; D005911:Gliosis / Q000276:immunology; D007108:Immune Tolerance; D007157:Immunologic Surveillance / Q000276:immunology*; D007166:Immunosuppressive Agents / Q000378:metabolism*; D008264:Macrophages / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008562:Membrane Glycoproteins / Q000037:antagonists & inhibitors / Q000276:immunology* / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL / Q000276:immunology / Q000378:metabolism / Q000601:surgery; D017628:Microglia / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D017211:Treatment Failure; D014407:Tumor Cells, Cultured / Q000276:immunology / Q000378:metabolism / Q000637:transplantation
D000911:Antibodies, Monoclonal; D000954:Antigens, Surface; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D007166:Immunosuppressive Agents; D008562:Membrane Glycoproteins