title: Interferon gamma enhances lymphokine-activated killer cell adhesion but not lysis of head and neck squamous cell carcinoma.
abstract: OBJECTIVE
  To determine if treatment with recombinant human interferon gamma (rHuIFN-gamma) increases the adhesion to, and lysis of, head and neck squamous cell carcinoma (SCC) cells by lymphokine-activated killer (LAK) and peripheral blood mononuclear (PBM) effector cells in vitro and to evaluate the role of cell surface adhesion molecules in these processes.
  
  
  METHODS
  Two human SCC cell lines, JHU-020-SCC and JHU-022-SCC, were used. Lymphokine-activated killer cells were generated by interleukin-2 stimulation of PBM cells obtained from the hemapheresis blood donor packs of healthy individuals. Adhesion assays were performed to assess the level of binding of both effector populations to SCC cells, which were treated with either fresh media or rHuIFN-gamma (100 U/mL). Binding was measured by flow cytometric detection of effector cells labeled with fluorescein-conjugated anti-CD45 monoclonal antibody. Monoclonal antibodies to the cell adhesion molecules HLA-DR, lymphocyte function-associated antigen 1, and intercellular adhesion molecule 1 were used in blocking experiments to determine their contribution to the process of effector-SCC cell adhesion. Cytotoxicity experiments were performed using a colorimetric assay to determine the cytotoxic response generated by LAK and PBM cells against SCC cells, with and without prior rHuIFN-gamma treatment of the tumor cells.
  
  
  METHODS
  Effector cell binding level and percent cytotoxicity of SCC cells.
  
  
  RESULTS
  Recombinant human interferon gamma treatment of JHU-020-SCC cells resulted in increased adhesion to both LAK cells and PBM cells (P < .001). The presence of anti-lymphocyte function-associated antigen 1 antibody resulted in elimination of the enhanced adhesion seen with rHuIFN-gamma pretreatment of SCC cells (P =.03), but antibody to intercellular adhesion molecule 1 and HLA-DR did not reduce the level of effector binding. The greatest cytotoxic response against both JHU-020-SCC and JHU-022-SCC was seen with LAK cells (P < or = .001). Pretreatment of tumor targets by rHuIFN-gamma (100 U/mL) resulted in no enhancement of cytotoxic response by either LAK or PBM cells; at the effector-target ratio of 30:1, there was a significant decrease in LAK cell-mediated cytotoxic response against rHuIFN-gamma-treated SCC cells (P < or = .02).
  
  
  CONCLUSIONS
  Recombinant human interferon gamma treatment of head and neck SCC cells does increase binding of both LAK cells and PBM cells to tumor cells, in part via the lymphocyte function-associated antigen 1 ligand mechanism. The cytotoxic effect mediated by LAK cells against head and neck SCC cells is reduced after rHuIFN-gamma treatment, suggesting that the activity of this cytokine may be more important in regulating antigen-specific cytotoxic response mediated by cytotoxic T-lymphocytes.
authors.affiliation: Division of Otolaryngology-Head and Neck Surgery, Duke University Medical Center, Durham, NC, USA.
authors.forename: R L
authors.initials: RL
authors.lastname: Scher
authors.forename: A
authors.initials: A
authors.lastname: Carras
authors.forename: D
authors.initials: D
authors.lastname: Schwab
authors.forename: W J
authors.initials: WJ
authors.lastname: Richtsmeier
authors.forename: W M
authors.initials: WM
authors.lastname: Koch
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology / Q000628:therapy*; D002448:Cell Adhesion / Q000187:drug effects; D015815:Cell Adhesion Molecules / Q000187:drug effects; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000276:immunology / Q000628:therapy*; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000494:pharmacology*; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects*; D007963:Leukocytes, Mononuclear / Q000187:drug effects; D011994:Recombinant Proteins / Q000494:pharmacology; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D015815:Cell Adhesion Molecules; D011994:Recombinant Proteins; D007371:Interferon-gamma