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 its effects on the in vitro mitogen responsiveness of peripheral blood mononuclear cells (PBMC) were investigated in cancer patients. Immunohistochemical studies showed LC1 expression in the cytoplasm of inflammatory cells morphologically recognized as a macrophage lineage, infiltrating the tumor interstices of gastric cancer. LC1 protein was detected in the ascitic fluid from gastric cancer patients using Western blot analysis. LC1 expression in PBMC was studied using a fluorescence-activated cell sorter (FACScan), which revealed that the percentage of CD14 and LC1 double positive cells was much greater in cancer patients than in healthy individuals. The proliferative response of PBMC by concanavalin A (ConA) stimulation was significantly suppressed in patients with advanced cancer, while the intact mitogen responsiveness in healthy individuals was inhibited when recombinant LC1 was added to the cultures. A similar inhibitory effect was induced by adding the supernatant of cancerous ascites or spleen cell cultures derived from advanced cancer patients. These inhibitory effects were eliminated, and the suppressed mitogen responsiveness in cancer patients recovered to the control level of healthy individuals when anti-LC1 antibody was added to the cultures. These findings indicate that LC1 is produced and expressed in cancer patients, and deeply involved in the immunosuppressive mechanism of tumor-bearing hosts.