Impaired proliferative response of V alpha 24 NKT cells from cancer patients against alpha-galactosylceramide.
Human invariant V alpha 24(+) NKT cells are a relatively new subpopulation of lymphocytes. It has been reported that V alpha 24 NKT cells are significantly involved in some human diseases. We have evaluated the number and function of V alpha 24 NKT cells in both healthy volunteers and cancer patients. In this study we found that V alpha 24 NKT cells in unfractionated PBMCs obtained from cancer patients did not respond efficiently to alpha-galactosylceramide (alpha-GalCer) in vitro. Thus, their proportion after stimulation with alpha-GalCer was smaller than that found in healthy volunteers. However, the cancer patients' V alpha 24 NKT cells retained cytotoxic activity against malignant target cells, and they could efficiently proliferate to alpha-GalCer when fractionated by sorting. Furthermore, we found that addition of G-CSF to the culture could restore the low proliferative response of V alpha 24 NKT cells from cancer patients. These results suggest that some functions of NKT cells in cancer patients are impaired, and this observation carries significant implications for immunotherapy-based cancer treatments.
Yanagisawa
Kazuhiko
K
Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
Seino
Ken-ichiro
K
Ishikawa
Yuriko
Y
Nozue
Mutsumi
M
Todoroki
Takeshi
T
Fukao
Katashi
K
D000276:Adjuvants, Immunologic / Q000494:pharmacology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002478:Cells, Cultured; D003602:Cytotoxicity, Immunologic / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005699:Galactosylceramides / Q000494:pharmacology*; D016179:Granulocyte Colony-Stimulating Factor / Q000494:pharmacology; D006801:Humans; D007376:Interleukin-2 / Q000494:pharmacology; D007694:Killer Cells, Natural / Q000276:immunology* / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000276:immunology / Q000378:metabolism; D008213:Lymphocyte Activation / Q000187:drug effects*; D018655:Lymphocyte Count; D008297:Male; D008875:Middle Aged; D009369:Neoplasms / Q000276:immunology*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000096:biosynthesis*; D016176:T-Lymphocyte Subsets / Q000276:immunology* / Q000378:metabolism
D000276:Adjuvants, Immunologic; D005699:Galactosylceramides; D007376:Interleukin-2; D016693:Receptors, Antigen, T-Cell, alpha-beta; D016179:Granulocyte Colony-Stimulating Factor