Immunosuppressive effect of shedding intercellular adhesion molecule 1 antigen on cell-mediated cytotoxicity against tumor cells.

We have examined whether shedding intercellular adhesion molecule-1 (ICAM-1) antigen from cultured tumors is able to inhibit the leukocyte function-associated antigen-1 (LFA-1)/ICAM-1 interaction between cytotoxic effector cells and ICAM-1+ target tumor cells. The cytotoxic activity of lymphokine-activated killer (LAK) cells incubated with spent media from ICAM-1+ tumor cells, especially interferon-gamma-stimulated tumor cells, was significantly decreased as compared with that of LAK cells treated with fresh culture medium without ICAM-1 antigen. Treatment of LAK cells with spent media from ICAM-1- tumor cells did not cause a significant decrease of the cytolytic activity towards ICAM-1+ tumor cells. These findings suggest that shedding of ICAM-1 antigen could be involved in binding of LFA-1 to LAK cells, resulting in reduced cytolytic activity.