Adhesion molecules on freshly recovered T leukemias promote tumor-directed lympholysis.
Besides facilitating cell to cell adhesion, the molecular interactions between CD2 and its ligand CD58 (lymphocyte function-associated antigen-3 [LFA-3]), as well as between CD11a/18 (LFA-1) and CD54 (intercellular adhesion molecule-1) have recently been recognized to participate in lymphocyte activation, recirculation, and effector function, including cytolytic activity towards tumor cells. We have investigated the role of CD2/CD58 and CD11a/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T-cell leukemias. The data support the notion that downregulation of CD54 and CD58 correlates with enhanced numbers of blasts in circulation and unsusceptibility to killing by autologous cytotoxic lymphocytes. Importantly, after induction of CD54 and CD58 expression on leukemic cells by recombinant cytokines such as tumor necrosis factor-alpha, tumor cells become highly susceptible to lymphocyte-mediated lysis in vitro. Our findings, therefore, stress the point that successful immunotherapy of malignant disease may be facilitated by influencing not only the immune response itself, but also adhesion molecules on the malignant tumor targets.
Abteilung Angewandte Immunologie, Institut für Radiologie und Pathophysiologie, Deutsches Krebsforschungszentrum, Heidelberg, Germany.
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D015703:Antigens, CD / Q000276:immunology; D000945:Antigens, Differentiation, T-Lymphocyte / Q000276:immunology; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules / Q000276:immunology*; D016207:Cytokines / Q000494:pharmacology; D003602:Cytotoxicity, Immunologic; D005455:Fluorescent Antibody Technique; D006801:Humans; D007111:Immunity, Cellular; D018799:Intercellular Adhesion Molecule-1; D015458:Leukemia, T-Cell / Q000276:immunology*; D011971:Receptors, Immunologic / Q000276:immunology; D016028:Receptors, Leukocyte-Adhesion / Q000276:immunology; D011994:Recombinant Proteins / Q000494:pharmacology; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology
D015703:Antigens, CD; D000945:Antigens, Differentiation, T-Lymphocyte; D018845:CD11 Antigens; D018821:CD18 Antigens; D018801:CD2 Antigens; D018968:CD58 Antigens; D015815:Cell Adhesion Molecules; D016207:Cytokines; D011971:Receptors, Immunologic; D016028:Receptors, Leukocyte-Adhesion; D011994:Recombinant Proteins; D018799:Intercellular Adhesion Molecule-1