Swainsonine augments the cytotoxicity of human lymphokine-activated killer cells against autologous thyroid cancer cells.
OBJECTIVE
Swainsonine (SW), an inhibitor of mammalian Golgi alpha-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.


METHODS
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-alpha-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.
Fujieda
S
S
Department of Oto-Rhino-Laryngology, Fukui Medical School, Japan.
Noda
I
I
Saito
H
H
Hoshino
T
T
Yagita
M
M
D000231:Adenocarcinoma, Papillary / Q000276:immunology*; D000276:Adjuvants, Immunologic / Q000494:pharmacology*; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D005455:Fluorescent Antibody Technique; D053804:Granzymes; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D015979:Killer Cells, Lymphokine-Activated / Q000187:drug effects / Q000201:enzymology / Q000276:immunology*; D012697:Serine Endopeptidases / Q000096:biosynthesis; D017026:Swainsonine / Q000494:pharmacology*; D013964:Thyroid Neoplasms / Q000276:immunology*; D014407:Tumor Cells, Cultured / Q000276:immunology
D000276:Adjuvants, Immunologic; D007376:Interleukin-2; D053804:Granzymes; D012697:Serine Endopeptidases; C509212:GZMA protein, human; D017026:Swainsonine