Reverse Translational Research for Understanding immune response in the Tumor and Identification of Biomarkers

2014 Fiscal Year Final Research Report

• Project/Area Number: 24501329
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Tumor immunology
• Research Institution: The University of Tokyo
• Principal Investigator: KAKIMI KAZUHIRO 東京大学, 医学部附属病院, 特任教授 (80273358)
• Co-Investigator(Kenkyū-buntansha): UEHA Satoshi 東京大学, 医学(系)研究科, 講師 (00447385) ; MATSUSHITA Hirokazu 東京大学, 医学部附属病院, 特任講師 (80597782)
• Project Period (FY): 2012-04-01 – 2015-03-31
• Keywords: CTL / 免疫抑制 / PD-1 / γδ T細胞 / 抗腫瘍免疫応答

Outline of Final Research Achievements

To develop novel effective cancer immunotherapy, we performed‘Reverse TR’ study using clinical samples and information from patients who received cancer immunotherapy at the University of Tokyo Hospital. To identify the biomarkers that can help us select patients who are expected to have benefit from immunotherapy, we integrate clinical study and basic immunological study. Many clinical samples were collected by NY-ESO-1 peptide or dendritic cell vaccines and γδ T cell transfer therapy. While some good clinical responses were obtained in certain patients, others did not show such clinical responses despite the induction of anti-tumor immune response. In murine model, we demonstrated that CTLs produce IFN-γ and mediate anti-tumor activity, but they simultaneously induce counter-regulatory immunosuppressive mechanisms in the tumor. These results suggest that strategies to regulate CTL-induced immunosuppressive microenvironment would improve the efficacy of cancer immunotherapy.

Free Research Field

腫瘍免疫学