To predict and improve the response to neoadjuvant chemotherapy in gastric cancer, targeting for immunological factor

2019 Fiscal Year Final Research Report

• Project/Area Number: 18K16308
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Urakawa Shinya 大阪大学, 医学系研究科, 特任助教(常勤) (40768975)
• Project Period (FY): 2018-04-01 – 2020-03-31
• Keywords: 術前化学療法 / Tim-3 / 胃がん / 食道がん / PD-1

Outline of Final Research Achievements

Immune cells extracted from pre- and post-neoadjuvant chemotherapy fresh tumor tissues in gastric cancer were analyzed by flow cytometry. The unique immune cells in CD8+ cells, which expressed only Tim-3, not PD-1, were found (Tim-3+ PD-1- in CD8+ cells). These immune cells showed higher expression of granzyme B and perforin than other cells. On the other hands, Tim-3+ PD-1- in CD8+ cells were not observed in esophageal tumor tissues after neoadjuvant chemotherapy. % PD-1+ Tim-3+ in CD8+ cells was conversely associated with the response to neoadjuvant chemotherapy. These cells showed low expression of granzyme B, perforin and IFN-g.
Our findings indicate that Tim-3+ PD-1- in CD8+ cells, which might have anti-tumor immunity, is specific to gastric tumor tissues or anti-cancer agents used for gastric cancer.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、特定条件下では、化学療法によって抗腫瘍効果をより有する細胞群が出現する可能性を示した。また、食道がんのようにTim-3分子を発現した細胞は、様々ながん種で予後不良の因子と報告されてきた。本研究の結果はこれらと異なるものであり、Tim-3分子の新しい知見につながる。現在、手術前もしくは手術後・再発後の治療選択肢として、免疫療法の導入が検討されており、予後改善に寄与する結果も出始めている。加えて、本研究は化学療法と免疫療法との併用が予後改善につながる可能性を示唆する。