RRC ID 42265
Author Konishi J, Yamazaki K, Yokouchi H, Shinagawa N, Iwabuchi K, Nishimura M.
Title The characteristics of human NKT cells in lung cancer--CD1d independent cytotoxicity against lung cancer cells by NKT cells and decreased human NKT cell response in lung cancer patients.
Journal Hum Immunol
Abstract The activation of human Valpha24+Vbeta11+natural killer T cells (NKT) cells (Valpha24 NKT cells) induces effective antitumor responses with secondary immune effects through activation of conventional T cells and natural killer cells. In this study, we attempted to analyze the characteristics of human NKT cells in lung cancer patients. Valpha24 NKT cells stimulated with alpha-GalCer from healthy volunteers exhibited direct cytotoxic activity against two (RERF-LC-OK and PC-3) of seven human lung cancer cell lines studied. Cytotoxicity by Valpha24 NKT cells against human lung cancer cells was dependent on the perforin pathway and independent of Fas/FasL pathway. Intracellular adhesion molecule (ICAM)-1 expression on tumor cells was clearly associated with the cytotoxicity of Valpha24 NKT cells. On the other hand, the proportion of Valpha24 NKT cells in the patients with lung cancer was lower than that in the healthy volunteers. Furthermore, the proliferative response of Valpha24 NKT cells to alpha-GalCer was significantly lower in the peripheral blood mononuclear cells in the patients with lung cancer. Addition of granulocyte colony-stimulating factor moderately restored the low proliferative response of Valpha24 NKT cells in the patients with lung cancer, however the percentage by which the response was restored in these patients was still lower than the natural response in healthy volunteers. These results suggest that Valpha24 NKT cells may play a pivotal role or the antitumor response in lung cancer.
Volume 65(11)
Pages 1377-88
Published 2004-11
DOI 10.1016/j.humimm.2004.09.003
PII S0198-8859(04)00623-8
PMID 15556688
MeSH Adult Aged Aged, 80 and over Antibodies, Monoclonal / pharmacology Antigens, CD / analysis Antigens, CD1 / immunology* Antigens, CD1d CD4-Positive T-Lymphocytes / chemistry CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / metabolism CD8-Positive T-Lymphocytes / chemistry CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / metabolism Cell Line, Tumor Cell Proliferation / drug effects Cytokines / metabolism Cytotoxicity Tests, Immunologic Cytotoxicity, Immunologic / immunology* Female Galactosylceramides / pharmacology Humans Killer Cells, Natural / chemistry Killer Cells, Natural / immunology* Killer Cells, Natural / metabolism Leukocytes, Mononuclear / drug effects Leukocytes, Mononuclear / immunology Leukocytes, Mononuclear / metabolism Lung Neoplasms / immunology* Lymphocyte Activation / drug effects Lymphocyte Activation / immunology Lymphocyte Subsets / chemistry Lymphocyte Subsets / immunology* Lymphocyte Subsets / metabolism Male Membrane Glycoproteins / antagonists & inhibitors Membrane Glycoproteins / metabolism Middle Aged Perforin Pore Forming Cytotoxic Proteins Receptors, Antigen, T-Cell, alpha-beta / analysis
IF 2.202
Times Cited 29
Human and Animal Cells