SWAINSONINE AUGMENTS THE CYTOTOXICITY OF HUMAN LYMPHOKINE-ACTIVATED KILLER-CELLS AGAINST AUTOLOGOUS THYROID-CANCER CELLS

Objective: Swainsonine (SW), an inhibitor of mammalian Golgi a-mannosi dase II, blocks the processing of high mannose to complex type oligosa ccharides. In this study, the effect of SW on the cytotoxicity of lymp hokine-activated killer (LAK) cells against autologous thyroid cancer was investigated. Design: Peripheral blood lymphocytes from patients w ith thyroid cancer were incubated with recombinant interleukin 2 (100 U/mL) and 0.5 mg/L of SW for 7 days, and thyroid cancer cells obtained from surgical specimens were pretreated with SW (0.5 mg/L) for 18 hou rs. The cytotoxicity of SW-treated LAK cells against tumor cells teste d in a standard 4-hour radioactive chromium Cr 51 release assay. Resul ts: The cytotoxicity of SW-treated LAK cells against autologous thyroi d cancer cells was found to be significantly greater than that of stan dard WK cells incubated with interleukin 2 alone. The N-alpha benzylox ycarbonyl-L-lysine thiobenzyl ester esterase activity of LAK cells, th is activity being a cytotoxic factor that is necessary for the lethal hit stage, was also increased by SW treatment. Further, thyroid cancer cells incubated with SW, as compared with nontreated tumor cells, sho wed much higher susceptibility to LAK killing. Conclusions: Our result s suggest that SW might have potential immunomodulatory properties in the treatment of thyroid cancer.