Inhibition of iNOS activity enhances the anti-tumor effects of alpha-galactosylceramide in cancer model

2015 Fiscal Year Final Research Report

• Project/Area Number: 25460679
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Laboratory medicine
• Research Institution: Gifu University
• Principal Investigator: Ito Hiroyasu 岐阜大学, 医学(系)研究科(研究院), 准教授 (80373075)
• Co-Investigator(Kenkyū-buntansha): SEISHIMA Mitsuru 岐阜大学, 大学院医学系研究科, 教授 (10171315) ; SHIRAKAMI Yohei 岐阜大学, 大学院医学系研究科, 助教 (50632816)
• Project Period (FY): 2013-04-01 – 2016-03-31
• Keywords: NKT細胞 / 腫瘍免疫 / 一酸化窒素 / 免疫抑制因子

Outline of Final Research Achievements

Alpha-garactosylceramide (GalCer) has anti-tumor effect in the basic research and clinical studies. However, anti-tumor effect of GalCer is limited. GalCer increases the production of IFN-γ which is involved in the suppression of tumor growth. On the other hand, the enhancement of IFN-γ production increases immunosuppressive factors such as nitric oxide (NO). This suppressive action might impair the anti-tumor effect. In the present study, we evaluated the anti-tumor effect of GalCer in the absence of inducible nitric oxide synthase (iNOS). In lung metastatic model, the number of tumor nodules in the lung of iNOS-KO mice treated with GalCer was significantly reduced compared with that in WT mice. The subcutaneous tumor experiments revealed that the administration of GalCer in the absence of iNOS expression enhanced the induction of tumor antigen-specific Th1 response. Our results indicated that the inhibition of iNOS expression could enhance the therapeutic efficacy of GalCer.

Free Research Field

免疫学