Document Detail


Lack of B7 expression, not human leukocyte antigen expression, facilitates immune evasion by human malignant gliomas.
MedLine Citation:
PMID:  17538388     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Lack of human leukocyte antigens and costimulatory molecules have been suggested as mechanisms by which human malignant gliomas avoid immune recognition and elimination. METHODS: Using quantitative multiparameter flow cytometric analysis, tumor cells from patients with glioblastoma multiforme (n = 18) were examined ex vivo for the expression of human leukocyte antigen Class I and II molecules and the costimulatory molecules B7-1 and B7-2. They were compared with reactive astrocytes from peritumoral brain metastases (n = 7), and astrocytes removed during nontumor surgery (n = 5). RESULTS: In contrast to the vast majority of solid peripheral human tumors, these results demonstrate that glioblastoma multiforme frequently express both human leukocyte antigen Class I and II molecules. Like most solid peripheral tumors, glioblastoma multiforme tumor cells express few or no B7 costimulatory molecules. Functional assays using heterogeneous ex vivo tumor preparations or pure populations of ex vivo tumor cells and microglia obtained using fluorescence-activated cell sorting indicate that CD4+ T-cells are activated by tumor cells only in the presence of exogenous B7 costimulation (provided by addition of soluble agonist anti-CD28 monoclonal antibody). CONCLUSION: Thus, in contrast to many solid peripheral tumors, failure to present tumor antigens is not a likely impediment to immunotherapeutic strategies against malignant gliomas. Rather, immunotherapeutic strategies need to overcome low levels of B7 costimulation.
Authors:
Richard C E Anderson; David E Anderson; James B Elder; Melandee D Brown; Christopher E Mandigo; Andrew T Parsa; Robert R Goodman; Guy M McKhann; Michael B Sisti; Jeffrey N Bruce
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Neurosurgery     Volume:  60     ISSN:  1524-4040     ISO Abbreviation:  Neurosurgery     Publication Date:  2007 Jun 
Date Detail:
Created Date:  2007-05-31     Completed Date:  2007-07-31     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  7802914     Medline TA:  Neurosurgery     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1129-36; discussion 1136     Citation Subset:  IM    
Affiliation:
Department of Neurological Surgery, The Neurological Institute, Columbia University College of Physicians and Surgeons, New York, New York 10032, USA. rca24@columbia.edu
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MeSH Terms
Descriptor/Qualifier:
Antigens, CD80 / metabolism*
Antigens, CD86 / metabolism*
Astrocytes / metabolism
Brain Neoplasms / metabolism*,  pathology,  secondary
Case-Control Studies
Flow Cytometry
Glioblastoma / metabolism*,  pathology
Histocompatibility Antigens Class I / metabolism*
Histocompatibility Antigens Class II / metabolism*
Humans
Chemical
Reg. No./Substance:
0/Antigens, CD80; 0/Antigens, CD86; 0/Histocompatibility Antigens Class I; 0/Histocompatibility Antigens Class II

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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