PMID- 16775224
OWN - NLM
STAT- MEDLINE
DCOM- 20061220
LR  - 20220408
IS  - 1522-8517 (Print)
IS  - 1523-5866 (Electronic)
IS  - 1522-8517 (Linking)
VI  - 8
IP  - 3
DP  - 2006 Jul
TI  - The role of human glioma-infiltrating microglia/macrophages in mediating 
      antitumor immune responses.
PG  - 261-79
AB  - Little is known about the immune performance and interactions of CNS 
      microglia/macrophages in glioma patients. We found that microglia/macrophages 
      were the predominant immune cell infiltrating gliomas ( approximately 1% of total 
      cells); others identified were myeloid dendritic cells (DCs), plasmacytoid DCs, 
      and T cells. We isolated and analyzed the immune functions of CD11b/c+CD45+ 
      glioma-infiltrating microglia/macrophages (GIMs) from postoperative tissue 
      specimens of glioma patients. Although GIMs expressed substantial levels of 
      Toll-like receptors (TLRs), they did not appear stimulated to produce 
      pro-inflammatory cytokines (tumor necrosis factor alpha, interleukin 1, or 
      interleukin 6), and in vitro, lipopolysaccharides could bind TLR-4 but could not 
      induce GIM-mediated T-cell proliferation. Despite surface major 
      histocompatibility complex class II expression, they lacked expression of the 
      costimulatory molecules CD86, CD80, and CD40 critical for T-cell activation. Ex 
      vivo, we demonstrate a corresponding lack of effector/activated T cells, as 
      glioma-infiltrating CD8+ T cells were phenotypically CD8+CD25-. By contrast, 
      there was a prominent population of regulatory CD4 T cells (CD4+CD25+FOXP3+) 
      infiltrating the tumor. We conclude that while GIMs may have a few intact innate 
      immune functions, their capacity to be stimulated via TLRs, secrete cytokines, 
      upregulate costimulatory molecules, and in turn activate antitumor effector T 
      cells is not sufficient to initiate immune responses. Furthermore, the presence 
      of regulatory T cells may also contribute to the lack of effective immune 
      activation against malignant human gliomas.
FAU - Hussain, S Farzana
AU  - Hussain SF
AD  - Department of Neurosurgery, The University of Texas M.D. Anderson Cancer Center, 
      P.O. Box 301402, Houston, TX 77230-1402, USA.
FAU - Yang, David
AU  - Yang D
FAU - Suki, Dima
AU  - Suki D
FAU - Aldape, Kenneth
AU  - Aldape K
FAU - Grimm, Elizabeth
AU  - Grimm E
FAU - Heimberger, Amy B
AU  - Heimberger AB
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20060614
PL  - England
TA  - Neuro Oncol
JT  - Neuro-oncology
JID - 100887420
RN  - 0 (Antibodies, Neoplasm)
RN  - 0 (Biomarkers, Tumor)
SB  - IM
MH  - Antibodies, Neoplasm/*biosynthesis/physiology
MH  - Antibody-Producing Cells/immunology/pathology
MH  - Antigen-Presenting Cells/*immunology/pathology
MH  - Biomarkers, Tumor/immunology
MH  - Brain Neoplasms/*immunology/pathology
MH  - Glioma/*immunology/pathology
MH  - Humans
MH  - Macrophages/*immunology/pathology
MH  - Microglia/*immunology/pathology
MH  - Neoplasm Invasiveness
PMC - PMC1871955
EDAT- 2006/06/16 09:00
MHDA- 2006/12/21 09:00
PMCR- 2007/07/01
CRDT- 2006/06/16 09:00
PHST- 2006/06/16 09:00 [pubmed]
PHST- 2006/12/21 09:00 [medline]
PHST- 2006/06/16 09:00 [entrez]
PHST- 2007/07/01 00:00 [pmc-release]
AID - 15228517-2006-008 [pii]
AID - neu0803p261 [pii]
AID - 10.1215/15228517-2006-008 [doi]
PST - ppublish
SO  - Neuro Oncol. 2006 Jul;8(3):261-79. doi: 10.1215/15228517-2006-008. Epub 2006 Jun 
      14.