Elucidation of the tumor immune response mechanism of upper gastrointestinal cancer through immune monitoring and establishment of individualized treatment

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K08776
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 55020:Digestive surgery-related
• Research Institution: Osaka University
• Principal Investigator: Tomoki Makino 大阪大学, 大学院医学系研究科, 助教 (80528620)
• Co-Investigator(Kenkyū-buntansha): 土岐 祐一郎 大阪大学, 大学院医学系研究科, 教授 (20291445)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 食道癌 / 3次リンパ様構造 / 腫瘍浸潤リンパ球 / PD-1抗体 / 胃癌

Outline of Final Research Achievements

As local immune monitoring, Immunoscore, which quantifies tumor-infiltrating T lymphocytes (TILs), was found useful in predicting the prognosis and response to preoperative chemotherapy in patients with esophageal squamous cell carcinoma (Noma T, Makino T, et al. Ann Surg 2021). Similarly, peritumoral tertiary lymphoid structures was identified to be useful in predicting prognosis and response to PD-1 antibody treatment for esophageal cancer (Hayashi Y, Makino T, etal. Br J Cancer 2023).
On the other hand, in the analysis of Nivolumab (IgG4)-bound peripheral blood T cells before and after administration of Nivolumab for esophageal cancer as systemic immune monitoring, the expression of CD103 on CD8(+) T cells was higher in Nivolumab responders compared with non-responders at 4 weeks after Nivolumab administration, and the CD103-high group showed better prognosis (in submission) .

Free Research Field

癌免疫微小環境

Academic Significance and Societal Importance of the Research Achievements

上部消化管癌において局所および全身の免疫モニタリングすることで、腫瘍免疫応答機序の（少なくとも)部分的な解明につながり、また患者予後や(化学療法、免疫療法を含む)治療効果予測に臨床上非常に有用であることが明らかとなった。いまだ研究途中の課題もあるが、今回得られた知見により上部消化管癌における個別化治療の確立、予後向上の一助となる可能性があり、その学術的・社会的意義は大きいものと考える。