Role of leukotriene B4 12-hydroxydehydrogenase in α-galactosylceramide-pulsed dendritic cell therapy for non-small cell lung cancer

• Published in: Biochemical and biophysical research communications 2018-11, Vol.506 (1), p.27-32
• Main Authors: Tanaka, Kazuhisa, Kanesaka, Yuri, Takami, Mariko, Suzuki, Akane, Hosokawa, Hiroyuki, Onodera, Atsushi, Kamata, Toshiko, Nagato, Kaoru, Nakayama, Toshinori, Yoshino, Ichiro, Motohashi, Shinichiro
• Format: Article
• Language: English
• Subjects: 60 APPLIED LIFE SCIENCES; Alcohol Oxidoreductases - genetics; Alcohol Oxidoreductases - immunology; ANTIGENS; BIOLOGICAL MARKERS; Carcinoma, Non-Small-Cell Lung - genetics; Carcinoma, Non-Small-Cell Lung - immunology; Carcinoma, Non-Small-Cell Lung - mortality; Carcinoma, Non-Small-Cell Lung - therapy; CD4+ T cell; CD4-Positive T-Lymphocytes - drug effects; CD4-Positive T-Lymphocytes - immunology; CD4-Positive T-Lymphocytes - pathology; CD8+ T cell; CD8-Positive T-Lymphocytes - drug effects; CD8-Positive T-Lymphocytes - immunology; CD8-Positive T-Lymphocytes - pathology; Dendritic Cells - cytology; Dendritic Cells - drug effects; Dendritic Cells - immunology; Dendritic Cells - transplantation; Dinoprostone - immunology; Dinoprostone - metabolism; Galactosylceramides - pharmacology; Gene Expression Regulation, Neoplastic; GLYCOLIPIDS; Granzymes - genetics; Granzymes - immunology; Humans; IMMUNOTHERAPY; Immunotherapy - methods; iNKT cell; INTERFERON; Interferon-gamma - genetics; Interferon-gamma - immunology; K562 Cells; LTB4DH; Lung Neoplasms - genetics; Lung Neoplasms - immunology; Lung Neoplasms - mortality; Lung Neoplasms - therapy; LUNGS; MESSENGER-RNA; Natural Killer T-Cells - drug effects; Natural Killer T-Cells - immunology; Natural Killer T-Cells - pathology; Perforin - genetics; Perforin - immunology; PGE2; Primary Cell Culture; PROSTAGLANDINS; RNA, Messenger - genetics; RNA, Messenger - immunology; Signal Transduction; Survival Analysis
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2018.10.048

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. •LTB4DH in CD4+ T cells rescued IFN-γ production with PGE2.•LTB4DH in CD8+ T cells rescued tumoricidal activity with PGE2.•LTB4DH in CD8+ T cells increased the expression of cytotoxic molecules with PGE2.