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Impaired proliferative response of V alpha 24 NKT cells from cancer patients against alpha-galactosylceramide
Authors:Yanagisawa Kazuhiko  Seino Ken-ichiro  Ishikawa Yuriko  Nozue Mutsumi  Todoroki Takeshi  Fukao Katashi
Institution:Department of Surgery, Institute of Clinical Medicine, University of Tsukuba, Tsukuba Science City, Ibaraki, Japan.
Abstract: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.
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