PMID- 15818597 OWN - NLM STAT- MEDLINE DCOM- 20051003 LR - 20220309 IS - 0894-1491 (Print) IS - 0894-1491 (Linking) VI - 51 IP - 4 DP - 2005 Sep TI - Impaired capacity for upregulation of MHC class II in tumor-associated microglia. PG - 279-85 AB - 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. CI - (c) 2005 Wiley-Liss, Inc. FAU - Schartner, Jill M AU - Schartner JM AD - Department of Neurological Surgery, University of Wisconsin School of Medicine, Madison, WI 53792-3232, USA. FAU - Hagar, Aaron R AU - Hagar AR FAU - Van Handel, Michelle AU - Van Handel M FAU - Zhang, Leying AU - Zhang L FAU - Nadkarni, Nivedita AU - Nadkarni N FAU - Badie, Behnam AU - Badie B LA - eng GR - CA14520-29/CA/NCI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Research Support, U.S. Gov't, P.H.S. PL - United States TA - Glia JT - Glia JID - 8806785 RN - 0 (Adjuvants, Immunologic) RN - 0 (CPG-oligonucleotide) RN - 0 (Histocompatibility Antigens Class II) RN - 0 (Inflammation Mediators) RN - 0 (Lipopolysaccharides) RN - 0 (Oligodeoxyribonucleotides) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Adjuvants, Immunologic/pharmacology MH - Animals MH - Brain Neoplasms/*immunology/metabolism/therapy MH - Cell Line MH - Encephalitis/chemically induced/*immunology/metabolism MH - Glioma/*immunology/metabolism/therapy MH - Gliosis/chemically induced/*immunology/metabolism MH - Histocompatibility Antigens Class II/drug effects/*immunology/metabolism MH - Immunotherapy/methods MH - Inflammation Mediators/pharmacology/therapeutic use MH - Interferon-gamma/pharmacology MH - Lipopolysaccharides/pharmacology MH - Macrophages/drug effects/immunology/metabolism MH - Microglia/drug effects/*immunology/metabolism MH - Oligodeoxyribonucleotides/pharmacology MH - Rats MH - Rats, Inbred F344 MH - Up-Regulation/drug effects/immunology EDAT- 2005/04/09 09:00 MHDA- 2005/10/04 09:00 CRDT- 2005/04/09 09:00 PHST- 2005/04/09 09:00 [pubmed] PHST- 2005/10/04 09:00 [medline] PHST- 2005/04/09 09:00 [entrez] AID - 10.1002/glia.20201 [doi] PST - ppublish SO - Glia. 2005 Sep;51(4):279-85. doi: 10.1002/glia.20201.