title: 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.
abstract: OBJECTIVE
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Hematology and Oncology, Department of Medicine, The University of Alabama at Birmingham, Birmingham, Alabama 35294, USA.
authors.forename: Zhiyong
authors.initials: Z
authors.lastname: Liu
authors.forename: Ben
authors.initials: B
authors.lastname: Guo
authors.forename: Richard D
authors.initials: RD
authors.lastname: Lopez
mesh_terms: D015703:Antigens, CD / Q000235:genetics / Q000276:immunology*; D018845:CD11 Antigens / Q000276:immunology; D018821:CD18 Antigens / Q000276:immunology; D002448:Cell Adhesion; D015815:Cell Adhesion Molecules / Q000235:genetics / Q000276:immunology*; D045744:Cell Line, Tumor; D018920:Coculture Techniques; D003602:Cytotoxicity, Immunologic; D015395:Histocompatibility Antigens Class I / Q000235:genetics; D006801:Humans; D007113:Immunity, Innate; D007167:Immunotherapy / Q000379:methods*; D018799:Intercellular Adhesion Molecule-1 / Q000235:genetics / Q000276:immunology*; D010190:Pancreatic Neoplasms / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology*; D014162:Transfection
chemical_list: D015703:Antigens, CD; D018845:CD11 Antigens; D018821:CD18 Antigens; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; C065289:ICAM2 protein, human; C099187:MHC class I-related chain A; C098080:MICB antigen; D016692:Receptors, Antigen, T-Cell, gamma-delta; D018799:Intercellular Adhesion Molecule-1