Impaired capacity for upregulation of MHC class II in tumor-associated microglia.
Immunotherapy for malignant gliomas is being studied as a possible adjunctive therapy for this highly fatal disease. Thus far, inadequate understanding of brain tumor immunology has hindered the design of such therapies. For instance, the role of microglia and macrophages, which comprise a significant proportion of tumor-infiltrating inflammatory cells, in the regulation of the local anti-tumor immune response is poorly understood. To study the response of microglia and macrophages to known activators in brain tumors, we injected CpG oligodeoxynucleotide (ODN), interferon-gamma (IFN-gamma), and IFN-gamma/LPS into normal and intracranial RG2 glioma-bearing rodents. Microglia/macrophage infiltration and their surface expression of MHC class II B7.1 and B7.2 was examined by flow cytometry. Each agent evaluated yielded a distinct microglia/macrophage response: CpG ODN was the most potent inducer of microglia/macrophage infiltration and B7.1 expression, while IFN-gamma resulted in the highest MHC-II expression in both normal and tumors. Regardless of the agent injected, however, MHC-II induction was significantly muted in tumor microglia/macrophage as compared with normal brain. These data suggest that microglia/macrophage responsiveness to activators can vary in brain tumors when compared with normal brain. Understanding the mechanism of these differences may be critical in the development of novel immunotherapies for malignant glioma.
Schartner
Jill M
JM
Department of Neurological Surgery, University of Wisconsin School of Medicine, Madison, WI 53792-3232, USA.
Hagar
Aaron R
AR
Van Handel
Michelle
M
Zhang
Leying
L
Nadkarni
Nivedita
N
Badie
Behnam
B
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000818:Animals; D001932:Brain Neoplasms / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D002460:Cell Line; D004660:Encephalitis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D005910:Glioma / Q000276:immunology* / Q000378:metabolism / Q000628:therapy; D005911:Gliosis / Q000139:chemically induced / Q000276:immunology* / Q000378:metabolism; D000949:Histocompatibility Antigens Class II / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D007167:Immunotherapy / Q000379:methods; D018836:Inflammation Mediators / Q000494:pharmacology / Q000627:therapeutic use; D007371:Interferon-gamma / Q000494:pharmacology; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D017628:Microglia / Q000187:drug effects / Q000276:immunology* / Q000378:metabolism; D009838:Oligodeoxyribonucleotides / Q000494:pharmacology; D051381:Rats; D011916:Rats, Inbred F344; D015854:Up-Regulation / Q000187:drug effects / Q000276:immunology
D000276:Adjuvants, Immunologic; C408982:CPG-oligonucleotide; D000949:Histocompatibility Antigens Class II; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; D009838:Oligodeoxyribonucleotides; D007371:Interferon-gamma