A set of genes associated with the interferon-γ response of lung cancer patients undergoing α-galactosylceramide-pulsed dendritic cell therapy.
Invariant natural killer T (iNKT) cells possess potent antitumor effects after activation with a specific glycolipid antigen, α-galactosylceramide (αGalCer). A phase I-II clinical study of αGalCer-pulsed dendritic cells (DC) to activate endogenous iNKT cells was previously performed in patients with non-small-cell lung cancer (NSCLC). In this clinical trial, the patients with increased interferon-γ (IFN-γ) production (>two-fold) in PBMC after the DC treatment (good responder group) experienced a prolonged overall survival time in comparison with the poor responder group. We extended the previous study and performed a microarray-based gene expression analysis using peripheral blood CD56(+) cells and CD56(-) CD3(+) T cells from patients enrolled in the above-mentioned clinical study. We sought to identify any biomarkers associated with the immune responses in this immunotherapy trial. Six patient samples corresponding to three subjects in the good responder group and three subjects in the poor responder group were included in the microarray analysis. Genes differentially expressed between pre-treatment and post-treatment samples were selected for analysis. Subsequently, genes that were only expressed in the good responder group or poor responder group were chosen. After these procedures, four selected genes were quantified by reverse transcriptase-polymerase chain reaction in another eight patient samples, and two genes, LTB4DH and DPYSL3, were confirmed to be candidate genes for the predictor of a good immune response. The expression profile of these two genes may be associated with the responsiveness of IFN-γ production after αGalCer-pulsed DC treatment.
Okita
Kohsuke
K
Department of Immunology, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba, Japan.
Motohashi
Shinichiro
S
Shinnakasu
Ryo
R
Nagato
Kaoru
K
Yamasaki
Kazuki
K
Sato
Yasunori
Y
Kitamura
Hiroshi
H
Hijikata
Atsushi
A
Yamashita
Masakatsu
M
Shimizu
Kanako
K
Fujii
Shin-Ichiro
S
Ohara
Osamu
O
Taniguchi
Masaru
M
Sakaida
Isao
I
Nakayama
Toshinori
T
D000328:Adult; D000368:Aged; D000429:Alcohol Oxidoreductases / Q000235:genetics*; D017252:CD3 Complex / Q000378:metabolism; D019002:CD56 Antigen / Q000378:metabolism; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D016000:Cluster Analysis; D003713:Dendritic Cells / Q000276:immunology / Q000637:transplantation; D005260:Female; D005699:Galactosylceramides / Q000276:immunology; D020869:Gene Expression Profiling; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D016219:Immunotherapy, Adoptive; D007371:Interferon-gamma / Q000378:metabolism; D008175:Lung Neoplasms / Q000276:immunology / Q000378:metabolism / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009124:Muscle Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016019:Survival Analysis; D013601:T-Lymphocytes / Q000276:immunology / Q000378:metabolism*
D017252:CD3 Complex; D019002:CD56 Antigen; C102926:DPYSL3 protein, human; D005699:Galactosylceramides; D009124:Muscle Proteins; D007371:Interferon-gamma; D000429:Alcohol Oxidoreductases; C082646:leukotriene B4 12-hydroxydehydrogenase
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