BIOLOGICAL RESPONSE MODIFIERS RENDER TUMOR-CELLS SUSCEPTIBLE TO AUTOLOGOUS EFFECTOR MECHANISMS BY INFLUENCING ADHESION RECEPTORS

Adhesion molecules such as CD2 and its ligand CD58 (LFA-3), as well as CD11a/18 (LFA-1) and CD54 (ICAM-1) regulate not only cell to cell att achment but also 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 interact ions in cellular immune responses directed towards freshly recovered h uman T cell leukemias. Downregulation of CD54 and CD58 were observed t o correlate with enhanced numbers of blasts in circulation and lack of susceptibility to killing by autologous cytotoxic lymphocytes. Furthe rmore, culturing tumor cells with recombinant TNF-alpha conditioned me dium resulted in reinduction of CD54 and CD58 expression and susceptib ility to lymphocyte mediated lysis in vitro. Our findings support the view that adhesion molecules play a pivotal role for tumor cell biolog y in vivo and stress the point that successful immunotherapy of malign ant disease may be facilitated by influencing not only the immune resp onse itself but also adhesion molecules on the malignant tumor targets .