Development of new and innovative cancer immunotherapy for gastric cancer

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K16440
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Gunma University
• Principal Investigator: Nakazawa Nobuhiro 群馬大学, 医学部附属病院, 助教 (60881290)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 胃癌 / TGFBI / 癌関連マクロファージ / 癌関連線維芽細胞 / 抗TGFBI抗体 / 免疫治療

Outline of Final Research Achievements

The origin of TGFBI secretion was demonstrated to be secreted by cancer-associated macrophages (CD163-positive cells) using multiple immunostaining. In a study of 197 resected specimens from gastric cancer surgery, high TGFBI expression was associated with significantly poorer prognosis, with high TGFBI expression accounting for a higher proportion of SE or greater depth and correlating with postoperative recurrence. Next, a multicenter study of 49 patients treated with Nivolumab for unresectable advanced recurrent gastric cancer between October 2017 and November 2018 at five participating centers showed that low expression of cancer stromal TGFBI was associated with higher sensitivity to Nivolumab treatment. The anti-TGFBI antibody, developed in collaboration with the University of Montpellier, is currently being used in basic experiments.

Free Research Field

消化管外科

Academic Significance and Societal Importance of the Research Achievements

切除不能進行再発胃癌に対する治療戦略として、現在NivolumabはHER2陰性胃癌では一次治療で、HER2陽性胃癌では三次治療以降で使用される薬剤であり、胃癌治療成績向上のためには欠かせないkey drugである。今回開発した抗TGFBI抗体を使用し、現在はex vivo研究で胃癌切除検体を使用して、抗TGFBI抗体とNivolumabの併用療法の意義について、基礎実験を施行している。抗TGFBI抗体がNivolumab感受性を亢進することができれば、切除不能進行再発胃癌症例の治療成績向上に寄与すると考えている。