Preserved IFN-alpha production of circulating Valpha24 NKT cells in primary lung cancer patients.
Human Valpha24 NKT cells bearing an invariant Valpha24JalphaQ antigen receptor, the counterpart of murine Valpha14 NKT cells, are activated by a specific ligand, alpha-GalCer, in a CD1d-dependent manner. Here, we demonstrate decreased numbers of circulating Valpha24 NKT cells in patients with primary lung cancer compared to healthy volunteers. However, Valpha24 NKT cells and DCs from lung cancer patients were functionally normal, even in the presence of tumor. Furthermore, levels of Valpha24 NKT cells in surgically resected lung tissue appeared to be equivalent to those of Valpha14 NKT cells in the mouse lung. Levels of Valpha24 NKT cells in the tumor tissue itself were increased about 2.5 times. Administration of alpha-GalCer-pulsed DCs expanded Valpha14 NKT cells in the lung more than 10 times, and the increased levels were sustained for 1 week. This may explain the previous finding that alpha-GalCer-pulsed DCs exerted strong antitumor activity in mouse lung tumor metastatic models. The potential use of alpha-GalCer-pulsed DCs for immunotherapy aimed at activating endogenous Valpha24 NKT cells in the lung of cancer patients is discussed.
Motohashi
Shinichiro
S
CREST (Core Research for Evolutional Science and Technology) Project, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Kobayashi
Seiichiro
S
Ito
Toshihiro
T
Magara
Kumiko K
KK
Mikuni
Osamu
O
Kamada
Noriaki
N
Iizasa
Toshihiko
T
Nakayama
Toshinori
T
Fujisawa
Takehiko
T
Taniguchi
Masaru
M
D000368:Aged; D000369:Aged, 80 and over; D017951:Antigen Presentation; D003713:Dendritic Cells / Q000502:physiology; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D006801:Humans; D016898:Interferon-alpha / Q000096:biosynthesis*; D007694:Killer Cells, Natural / Q000276:immunology*; D008175:Lung Neoplasms / Q000276:immunology*; D008297:Male; D008875:Middle Aged
D005699:Galactosylceramides; D016898:Interferon-alpha