Document Detail

B7.1 on human carcinomas: costimulation of T cells and enhanced tumor-induced T-cell death.
MedLine Citation:
PMID:  10831322     Owner:  NLM     Status:  MEDLINE    
Human squamous cell carcinomas of the head and neck (SCCHN) do not express the costimulatory molecules B7.1 or B7.2 in situ or in culture. Transduction of B7.1(-) SCCHN cells with the retroviral B7. 1 and neo(r) genes resulted in the expression of high levels of the transgene in these tumor cells. When B7.1(+) SCCHN cells were used as stimulators of autologous or allogeneic PBL in mixed lymphocyte-tumor cultures (MLTC), T-cell proliferation and generation of antitumor effector T cells as well as levels of their lytic activity were significantly increased. At the same time, a proportion of activated T cells seen to undergo apoptosis was found to be significantly higher upon coincubation with B7.1(+) SCCHN than with B7.1(-) SCCHN. Both B7.1(+) and B7.1(-) SCCHN cells were found to express FasL on the cell surface and in the cytoplasm, as well as mRNA for FasL and mRNA for TRAIL. However, expression of the B7.1 transgene did not lead to increased expression of FasL protein on tumor cells. Yet, up to 50% of activated CD28(+) allogeneic T cells, which were CD95(+), showed evidence of DNA fragmentation in JAM and TUNEL assays upon incubation with an excess of B7.1(+) SCCHN for 24 h. Tumor-induced T-cell death was equally and only in part blocked by anti-Fas antibodies in both B7.1(+) and B7.1(-) MLTC. While surface expression of B7.1 molecules on SCCHN cells enhanced T-cell costimulation via B7.1-CD28 interactions, it did not rescue activated T cells from tumor-induced apoptosis. The outcome of MLTC under these conditions was dependent on the ratio of tumor to T cells. Thus, in the presence of an excess of B7.1(+) tumor cells, activated T cells showed increased sensitivity to apoptosis which did not appear to be Fas/FasL mediated. These data are important for the development of B7.1 gene therapy and efforts directed at the generation of effector cells in MLTC.
S Lang; Y Atarashi; Y Nishioka; J Stanson; N Meidenbauer; T L Whiteside
Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  Cellular immunology     Volume:  201     ISSN:  0008-8749     ISO Abbreviation:  Cell. Immunol.     Publication Date:  2000 May 
Date Detail:
Created Date:  2000-07-13     Completed Date:  2000-07-13     Revised Date:  2007-11-14    
Medline Journal Info:
Nlm Unique ID:  1246405     Medline TA:  Cell Immunol     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  132-43     Citation Subset:  IM    
Copyright Information:
Copyright 2000 Academic Press.
Department of Pathology, University of Pittsburgh Cancer Institute, PA 15213, USA.
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MeSH Terms
Antigens, CD80 / genetics,  immunology*
Antigens, CD95 / metabolism
Carcinoma, Squamous Cell / immunology*
Coculture Techniques
Cytotoxicity, Immunologic
Fas Ligand Protein
Head and Neck Neoplasms / immunology
Lymphocyte Activation
Membrane Glycoproteins / metabolism
Signal Transduction
T-Lymphocytes / immunology*
T-Lymphocytes, Cytotoxic
Transformation, Genetic
Tumor Cells, Cultured
Grant Support
Reg. No./Substance:
0/Antigens, CD80; 0/Antigens, CD95; 0/FASLG protein, human; 0/Fas Ligand Protein; 0/Membrane Glycoproteins

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