Document Detail

Expression of intercellular adhesion molecule (ICAM)-1 or ICAM-2 is critical in determining sensitivity of pancreatic cancer cells to cytolysis by human gammadelta-T cells: implications in the design of gammadelta-T-cell-based immunotherapies for pancreatic cancer.
MedLine Citation:
PMID:  19175829     Owner:  NLM     Status:  MEDLINE    
BACKGROUND AND AIMS: gammadelta-T cells can recognize and kill malignant cells, particularly those of epithelial origin, through mechanisms which do not require the recognition of tumor-specific antigens (innate immune response). This natural ability of gammadelta-T cells to kill tumor cells in a tumor antigen-independent manner provides a strong rationale for developing clinical trials designed to exploit the innate antitumor properties of gammadelta-T cells.
METHODS: In vitro studies were carried out to asses the sensitivity of pancreatic cancer cells (MIA PaCa2, BxPC-3, PANC-1) to killing by ex vivo expanded human gammadelta-T cells.
RESULTS: The capacity of gammadelta-T cells to bind to as well as to kill pancreatic cancer cells correlated with the degree of surface expression of key intercellular adhesion molecules (ICAM) present on pancreatic cancer cells. Moreover, pancreatic cancer cells expressing neither ICAM-1 nor ICAM-2 were bound poorly by gammadelta-T cells and were found to be resistant to gammadelta-T-cell killing. However, upon transfection of resistant cells with ICAM-1 or ICAM-2, gammadelta-T cells were then able to bind to and subsequently kill these cells.
CONCLUSION: In vitro, the expression of ICAM-1 or ICAM-2 on human pancreatic cancer cells is critically important in determining the extent to which these cells are sensitive to killing by human gammadelta-T cells. Accordingly, in ongoing and future clinical studies using gammadelta-T cells for the treatment of a variety of epithelial-derived solid tumors-including pancreatic cancer-interventions intended to modulate ICAM expression on tumor cells may become important adjuncts to gammadelta-T-cell-based immunotherapies.
Zhiyong Liu; Ben Guo; Richard D Lopez
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Publication Detail:
Type:  Journal Article     Date:  2008-11-03
Journal Detail:
Title:  Journal of gastroenterology and hepatology     Volume:  24     ISSN:  1440-1746     ISO Abbreviation:  J. Gastroenterol. Hepatol.     Publication Date:  2009 May 
Date Detail:
Created Date:  2009-08-03     Completed Date:  2009-10-15     Revised Date:  2013-02-25    
Medline Journal Info:
Nlm Unique ID:  8607909     Medline TA:  J Gastroenterol Hepatol     Country:  Australia    
Other Details:
Languages:  eng     Pagination:  900-11     Citation Subset:  IM    
Division of Hematology and Oncology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
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MeSH Terms
Antigens, CD / genetics,  immunology*
Antigens, CD11 / immunology
Antigens, CD18 / immunology
Cell Adhesion
Cell Adhesion Molecules / genetics,  immunology*
Cell Line, Tumor
Coculture Techniques
Cytotoxicity, Immunologic*
Histocompatibility Antigens Class I / genetics
Immunity, Innate*
Immunotherapy / methods*
Intercellular Adhesion Molecule-1 / genetics,  immunology*
Pancreatic Neoplasms / genetics,  immunology,  pathology,  therapy*
Receptors, Antigen, T-Cell, gamma-delta / immunology*
T-Lymphocytes / immunology*
Reg. No./Substance:
0/Antigens, CD; 0/Antigens, CD11; 0/Antigens, CD18; 0/Cell Adhesion Molecules; 0/Histocompatibility Antigens Class I; 0/ICAM2 protein, human; 0/MHC class I-related chain A; 0/MICB antigen; 0/Receptors, Antigen, T-Cell, gamma-delta; 126547-89-5/Intercellular Adhesion Molecule-1

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