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.