Immunotherapy targeting Tim-3+ PD-1- CD8+ cells in colorectal cancer

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18088
• 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: Kitakaze Masatoshi 大阪大学, 医学部附属病院, 医員 (30835252)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 大腸癌 / 正常粘膜 / tim-3単独発現細胞 / PD-1 / 腸内細菌 / 抗腫瘍免疫

Outline of Final Research Achievements

Immune cells extracted from fresh tumor tissues and normal tissues in colorectal cancer patients were analyzed by flow cytometry. The unique immune cells in CD8+ cells, which expressed only Tim-3, not PD-1 (Tim-3+ PD-1- in CD8+ cells), were found more frequently in normal tissues. On the other hand, these immune cells were not observed in normal tissues of other organs such as the esophagus and stomach.
Tim-3+ PD-1- CD8+ cells in some cases showed higher productivity of IFN-γ than other cells. 　On the contrary, these immune cells were not associated with clinicopathological factors such as the tumor location, progression, and prognosis except for age.
Our findings indicate that Tim-3+ PD-1- in CD8+ cells, which might have anti-tumor immunity, is specific to colon normal tissues. Further studies should be warranted to investigate how these immune cells are generated and have an influence on colorectal cancer cells.

Free Research Field

消化器外科

Academic Significance and Societal Importance of the Research Achievements

本研究の結果は、大腸内の正常組織に抗腫瘍効果を有する特異的細胞群が存在することを示した。これら細胞群は、他臓器の正常組織にほとんど存在しないことから、腸内細菌が発生メカニズムの一つである可能性がある。また、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おり、本研究の結果はこれまでの報告と異なるものであり、Tim-3分子の新しい知見となる。