The development and characterization of a natural killer cell-resistant human renal cell carcinoma cell line.
Natural killer (NK) cells are large granular lymphocytes that are able to recognize and lyse a broad spectrum of transformed cells. We report one approach to identify NK surface recognition molecules on human tumor targets. A cloned renal cell carcinoma (RCC) cell line, 5117GB, sensitive to NK activity, was made NK-resistant (5117GBT) by exposure to peripheral blood mononuclear cells. Both cell lines were found to be sensitive to lymphokine-activated killer cells. Both 5117GB and 5117GBT were positive for laminin (25-33%), CD2 (LFA-3 receptor, 95-98%), CD54 (ICAM-1, 99-100%) and CD58 (LFA-3, 100%). 5117GB was positive for HLA-ABC while 5117GBT lost detectable HLA-ABC. F(ab')2 fragments of HLA-ABC were not able to block NK-mediated cytotoxicity of 5117GB. We identified 6 murine monoclonal antibodies that preferentially bind either to sensitive or resistant RCC cells. The role of each of the antigens recognized by these antibodies in NK-mediated lysis is being explored. The development of NK-sensitive and NK-resistant human solid tumor cell lines may allow further exploration of surface molecules involved with NK binding and lysis.
Ernstoff
M S
MS
Department of Medicine, University of Pittsburgh, Pa.
Jaffee
E M
EM
Oeler
T
T
D000945:Antigens, Differentiation, T-Lymphocyte / Q000096:biosynthesis; D018801:CD2 Antigens; D015815:Cell Adhesion Molecules / Q000096:biosynthesis; D002460:Cell Line; D003601:Cytotoxicity Tests, Immunologic; D004797:Enzyme-Linked Immunosorbent Assay; D005434:Flow Cytometry; D015395:Histocompatibility Antigens Class I; D006801:Humans; D018799:Intercellular Adhesion Molecule-1; D007680:Kidney Neoplasms / Q000276:immunology*; D015979:Killer Cells, Lymphokine-Activated / Q000276:immunology; D007694:Killer Cells, Natural / Q000276:immunology*; D007797:Laminin / Q000096:biosynthesis; D011971:Receptors, Immunologic / Q000096:biosynthesis
D000945:Antigens, Differentiation, T-Lymphocyte; D018801:CD2 Antigens; D015815:Cell Adhesion Molecules; D015395:Histocompatibility Antigens Class I; D007797:Laminin; D011971:Receptors, Immunologic; D018799:Intercellular Adhesion Molecule-1