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Shigeharu Fujieda, MD; Ichiro Noda, MD; Hitoshi Saito, MD; Takashi Hoshino, MD; Masato Yagita, MD

Arch Otolaryngol Head Neck Surg. 1994;120(4):389-394.

Abstract
Objective
Swainsonine (SW), an inhibitor of mammalian Golgi -mannosidase II, blocks the processing of high mannose to complex type oligosaccharides. In this study, the effect of SW on the cytotoxicity of lymphokine-activated killer (LAK) cells against autologous thyroid cancer was investigated.

Design
Peripheral blood lymphocytes from patients with 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 hours. The cytotoxicity of SW-treated LAK cells against tumor cells tested in a standard 4-hour radioactive chromium Cr 51 release assay.

Results
The cytotoxicity of SW-treated LAK cells against autologous thyroid cancer cells was found to be significantly greater than that of standard LAK cells incubated with interleukin 2 alone. The N--benzyloxycarbonyl–L-lysine thiobenzyl ester esterase activity of LAK cells, this 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, showed much higher susceptibility to LAK killing.

Conclusions
Our results suggest that SW might have potential immunomodulatory properties in the treatment of thyroid cancer.

(Arch Otolaryngol Head Neck Surg. 1994;120:389-394)

Author Affiliations
From the Departments of Oto-Rhino-Laryngology (Drs Fujieda, Noda, and Saito) and Immunology and Parasitology (Drs Hoshino and Yagita), Fukui (Japan) Medical School, and the Department of Internal Medicine (Dr Yagita), Kitano Hospital, Tazuke-Kofukai Medical Research Institute, Osaka, Japan. Dr Fujieda is now with the Department of Medicine, Division of Clinical Immunology and Allergy, University of California–Los Angeles.

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