Biomarker research for PD-1 inhibitor and new combination therapy anti-PD-1 and chemotherapeutic agents

2015 Fiscal Year Final Research Report

• Project/Area Number: 26670583
• Research Category: Grant-in-Aid for Challenging Exploratory Research
• Allocation Type: Multi-year Fund
• Research Field: General surgery
• Research Institution: Kyushu University
• Principal Investigator: Maehara Yoshihiko 九州大学, 医学(系)研究科(研究院), 教授 (80165662)
• Co-Investigator(Kenkyū-buntansha): IKEDA Tetsuo 九州大学, 大学病院, 准教授 (60585701) ; KAWANAKA Hirofumi 国立病院機構別府医療センター, その他, 臨床研究部長 (10363334) ; OKI Eiji 九州大学, 大学病院, 講師 (70380392) ; OKANO Shinji (10380429)
• Project Period (FY): 2014-04-01 – 2016-03-31
• Keywords: 免疫チェックポイント阻害剤 / 大腸癌 / バイオマーカー / PD-1 / PD-L1

Outline of Final Research Achievements

The treatment of anti-PD-1 antibody and chemotherapy, FOLFIRI, showed synergistic tumor growth inhibition in wild type mice. The anti-tumor effects of anti-PD-1 antibody were cancelled in the Balb/c nude mice, suggesting the anti-tumor effects were dependet on T cells. Interestingly, PD-1-sensitive naturally occurring tumor reactive T cells were induced in unteated mice bearing CT26. On the other hand, high dose release of tumor antigens from cancer cells destructed by chemotherapy could induce a number of PD-1/PD-L1-insensitive tumor reactive T cells in lymphoid organs. Furthermore, we found that in vivo anti-PD-1 antibody treatment had a novel effect; the recruitment of effector T cells in the tumor sites, in addition to local suppression of the effector function of T cells.

Free Research Field

消化器外科