Adhesion molecules such as CD2 and its ligand CD58 (LFA-3), as well as CD1 la/18 (LFA-1) and CD54 (ICAM-1) regulate not only cell to cell attachment 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 CDlla/18/CD54 interactions in cellular immune responses directed towards freshly recovered human T cell leukemias. Downregulation of CD54 and CD58 were observed to correlate with enhanced numbers of blasts in circulation and lack of susceptibility to killing by autologous cytotoxic lymphocytes. Furthermore, culturing tumor cells with recombinant TNF-alpha conditioned medium resulted in reinduction of CD54 and CD58 expression and susceptibility to lymphocyte mediated lysisin vitro. Our findings support the view that adhesion molecules play a pivotal role for tumor cell biologyin vivoand 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.