Regulatory mechanisms of anti-tumor immunity by inhibitory coreceptor, LAG-3

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K16694
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49070:Immunology-related
• Research Institution: The University of Tokyo
• Principal Investigator: Maruhashi Takumi 東京大学, 定量生命科学研究所, 助教 (60743961)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 免疫チェックポイント分子 / LAG-3 / がん免疫 / ヘルパーT細胞

Outline of Final Research Achievements

Lymphocyte activation gene-3 (LAG-3), one of the immune checkpoint molecules, expected as the foremost target next to PD-1 and CTLA-4 in the development of cancer immunotherapy. In this study, I investigated the involvement of LAG-3 in the regulation of immune responses against cancer and tried to elucidate the underlying mechanism.
Genetic deletion of LAG-3 exhibited therapeutic effects against tumor growth in several mouse models, which was accompanied by elevated cytokine production from tumor-infiltrating CD4-positive helper T (Th) cells. These results strongly suggest that LAG-3 contributes to immune escape mechanisms in tumors by regulating the activation of tumor-specific Th cells.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究成果は、ヘルパーT細胞による免疫監視機構およびがん細胞がLAG-3を介してその監視機構を回避する新たなメカニズムの一端を明らかにしたものである。また、LAG-3を標的としたヘルパーT細胞活性化制御法、そしてヘルパーT細胞を介したがん免疫応答賦活化という、今までに無い視点のがん免疫療法の開発につながる可能性があり、既存のがん免疫療法に抵抗性のがん腫、患者においても効果を示す可能性があるだけでなく、既存のがん免疫療法と併用することで奏効率の大幅な向上につながることが期待される。