Impacts of central tolerance against tumor antigen on anti-tumor immune responses

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21537
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Chiba University
• Principal Investigator: Kimura Motoko 千葉大学, 大学院医学研究院, 教授 (00345018)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: 中枢性免疫寛容 / 抗腫瘍免疫 / 胸腺 / がん抗原 / 腫瘍微小環境

Outline of Final Research Achievements

Our body has a great immune system to attack cancer; however, our immune system often become exhausted, allowing cancer development. Cancer immunotherapy utilizes this phenomenon and boosts our immune system to attack cancer. Therefore, it would be very important to understand the mechanism why our immune system become tolerant to cancer. Most research has focused on immune responses in tumor microenvironment, whereas we think it is essential to know how our immune system respond to cancer in our whole body. In this study, we focused on central tolerance against cancer. We first analyzed the thymus of tumor bearing mice and found that a specific subset of dendritic cells (DCs) was increased in the thymus. Importantly, the DC subset seemed to be migrated from the tumor site and bring tumor antigens to the thymus. We are currently performing an RNA-seq analysis to figure out the characteristic features of this specific DCs and analyzing the outcome of thymocyte development.

Free Research Field

免疫学、腫瘍免疫学

Academic Significance and Societal Importance of the Research Achievements

昨今の腫瘍に対する免疫療法の開発は目覚ましい。特に、免疫チェックポイント阻害剤の驚異的な効果から、患者自身の免疫システムを活性化することにより腫瘍を攻撃する「免疫療法」は、今後、さらに大きく発展する可能性を秘めている。本研究成果は、抗腫瘍免疫応答の問題点である「がんへの免疫寛容の成立」機構のうち、これまであまり研究が進んでいない「がん抗原に対する中枢性免疫寛容」が、がんへの免疫応答へ及ぼす影響について解析した。とくに胸腺機能が活発な小児のがんに対する治療戦略を考える上で、重要な知見が得られた。