Effect of combination of IL-18 and immune checkpoint inhibitors on peritoneal dissemination of tumor cells

2016 Fiscal Year Final Research Report

• Project/Area Number: 24390306
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Partial Multi-year Fund
• Section: 一般
• Research Field: General surgery
• Research Institution: Hyogo Medical University
• Principal Investigator: Okamura Haruki 兵庫医科大学, 医学部, 教授 (60111043)
• Co-Investigator(Kenkyū-buntansha): 笹子 三津留 兵庫医科大学, 医学部, 教授 (40143490) ; 菊池 正二郎 兵庫医科大学, 医学部, 准教授 (70381960) ; 前山 義博 兵庫医科大学, 医学部, 非常勤講師 (80614031) ; 田中 義正 長崎大学, 医歯(薬)学総合研究科, 准教授 (90280700)
• Research Collaborator: LI Wen ; MA Zhifeng ; Yosif El-Darawish ; SEKI Hatsuka
• Project Period (FY): 2012-04-01 – 2017-03-31
• Keywords: IL-18 / 免疫チェックポイント阻害薬 / 抗CTLA4抗体 / 抗PD-L1抗体 / NK細胞 / Treg / CD8陽性T細胞

Outline of Final Research Achievements

This study was carried out on the trial to examine the utility of interleukin-18 (IL-18) for cancer immunotherapy. Recent development of immune checkpoint inhibitors targeting PD-1 or PD-L1 for cancer immunotherapy have made a breakthrough and opened new era in cancer therapy. This therapy requires further progress in augmentation of efficacy and suppression of adverse events. Using an animal model of cancer peritoneal dissemination, we demonstrated that IL-18 markedly augments the efficacy of immune checkpoint inhibitors suppressing tumor growth and prolonging survival of mice inoculated with tumor cells. As a mechanism, it was considered that IL-18 strongly enhances expansion of effector cells including NK cells, γδ T cells, and CD8+ T cells, and oppositely suppresses Treg cells. These results demonstrated utility of IL-18 in cancer immunotherapy and suggested usage of IL-18 for wider range of immunotherapy.

Free Research Field

腫瘍免疫制御学