ENHANCED EXPRESSION OF LIPOCORTIN-1 AS A NEW IMMUNOSUPPRESSIVE PROTEIN IN CANCER-PATIENTS AND ITS INFLUENCE ON REDUCED IN-VITRO PERIPHERAL-BLOOD LYMPHOCYTE-RESPONSE TO MITOGENS

To clarify the mechanism of immunosuppression in cancer-bearing hosts, the expression of lipocortin-1 (LC1), a new immunosuppressant, and it s effects on the in vitro mitogen responsiveness of peripheral blood m ononuclear cells (PBMC) were investigated in cancer patients. Immunohi stochemical studies showed LC1 expression in the cytoplasm of inflamma tory cells morphologically recognized as a macrophage lineage, infiltr ating the tumor interstices of gastric cancer. LC1 protein was detecte d in the ascitic fluid from gastric cancer patients using Western blot analysis. LC1 expression in PBMC was studied using a fluorescence-act ivated cell sorter (FACScan), which revealed that the percentage of CD 14 and LC1 double positive cells was much greater in cancer patients t han in healthy individuals. The proliferative response of PBMC by conc anavalin A (ConA) stimulation was significantly suppressed in patients with advanced cancer, while the intact mitogen responsiveness in heal thy individuals was inhibited when recombinant LC1 was added to the cu ltures. A similar inhibitory effect was induced by adding the supernat ant of cancerous ascites or spleen cell cultures derived from advanced cancer patients. These inhibitory effects were eliminated, and the su ppressed mitogen responsiveness in cancer patients recovered to the co ntrol level of healthy individuals when anti-LC1 antibody was added to the cultures. These findings indicate that LC1 is produced and expres sed in cancer patients, and deeply involved in the immunosuppressive m echanism of tumor-bearing hosts.