RRC ID 54149
Author Tanaka K, Kanesaka Y, Takami M, Suzuki A, Hosokawa H, Onodera A, Kamata T, Nagato K, Nakayama T, Yoshino I, Motohashi S.
Title Role of leukotriene B4 12-hydroxydehydrogenase in α-galactosylceramide-pulsed dendritic cell therapy for non-small cell lung cancer.
Journal Biochem Biophys Res Commun
Abstract Invariant natural killer T (iNKT) cells exhibit potent antitumor effects upon activation by recognizing a specific glycolipid antigen. We previously performed phase I-II clinical studies to utilize iNKT cells using α-galactosylceramide-pulsed dendritic cells and identified leukotriene B4 12-hydroxydehydrogenase (LTB4DH) as a biomarker highly expressed in T cells derived from non-small cell lung cancer (NSCLC) patients who showed prolonged survival in respond to the iNKT cell immunotherapy. Because LTB4DH expression correlated with prolonged survival of NSCLC patients, we considered LTB4DH to play a role in iNKT cell immunotherapy. We herein demonstrate that the overexpression of LTB4DH in CD4+ or CD8+ T cells increases interferon-γ production and tumoricidal activity in the presence of prostaglandin E2. Moreover, the expression of granzyme a, granzyme b, and perforin mRNA was increased in LTB4DH-overexpressing cells.
Volume 506(1)
Pages 27-32
Published 2018-11-17
DOI 10.1016/j.bbrc.2018.10.048
PII S0006-291X(18)32194-6
PMID 30336981
MeSH Alcohol Oxidoreductases / genetics* Alcohol Oxidoreductases / immunology CD4-Positive T-Lymphocytes / drug effects CD4-Positive T-Lymphocytes / immunology CD4-Positive T-Lymphocytes / pathology CD8-Positive T-Lymphocytes / drug effects CD8-Positive T-Lymphocytes / immunology CD8-Positive T-Lymphocytes / pathology Carcinoma, Non-Small-Cell Lung / genetics Carcinoma, Non-Small-Cell Lung / immunology Carcinoma, Non-Small-Cell Lung / mortality Carcinoma, Non-Small-Cell Lung / therapy* Dendritic Cells / cytology Dendritic Cells / drug effects Dendritic Cells / immunology* Dendritic Cells / transplantation Dinoprostone / immunology Dinoprostone / metabolism Galactosylceramides / pharmacology* Gene Expression Regulation, Neoplastic* Granzymes / genetics Granzymes / immunology Humans Immunotherapy / methods Interferon-gamma / genetics Interferon-gamma / immunology K562 Cells Lung Neoplasms / genetics Lung Neoplasms / immunology Lung Neoplasms / mortality Lung Neoplasms / therapy* Natural Killer T-Cells / drug effects Natural Killer T-Cells / immunology Natural Killer T-Cells / pathology Perforin / genetics Perforin / immunology Primary Cell Culture RNA, Messenger / genetics RNA, Messenger / immunology Signal Transduction Survival Analysis
IF 2.985
Times Cited 0
DNA material pCAG-HIVgp (RDB04394) pCMV-VSV-G-RSV-Rev (RDB04393)