Evaluation of Tr2 cells to maximize the efficiency of PD-1 blockade in tumor immunity

2022 Fiscal Year Final Research Report

• Project/Area Number: 19K16881
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 50020:Tumor diagnostics and therapeutics-related
• Research Institution: Kyoto University (2020-2022); Foundation for Biomedical Research and Innovation at Kobe (2019)
• Principal Investigator: Tajima Masaki 京都大学, 医学研究科, 助教 (50815032)
• Project Period (FY): 2019-04-01 – 2023-03-31
• Keywords: 腫瘍免疫 / 免疫代謝 / IL-10 / Dectin-1

Outline of Final Research Achievements

Immune checkpoint blockade is one of the most promising therapeutic applications for treating cancer patients. However, managing the risk of immune-related adverse effects (irAE) in these patients is essential for maximal anti-tumor responses. In this study, the potent immunosuppressive function of IL-10-producing CD4+ T cell subset (Tr2) to ameliorate irAEs was evaluated by using tumor-bearing NOD mice injected with PD-1 blocking antibody, which develops severe type-1 diabetes. By activating IL-4/STAT6/GATA3 pathway together with a-KG/mTOR/CEBPb　pathway by Zymosan-Depleted (Dectin-1 ligand) injection, these mice showed strong resistance to type-1 diabetes compared to control, without any negative effect on anti-tumor responses. This suggests the therapeutic potential of Tr2 cells for treating irAEs in cancer patients under immune checkpoint therapy.

Free Research Field

腫瘍免疫

Academic Significance and Societal Importance of the Research Achievements

本研究では、免疫関連副作用によって免疫チェックポイント阻害治療が制限されてしまう癌患者において、抗腫瘍効果が担保された上で自己免疫応答が抑制可能な治療アプローチの可能性を示すことができた。また、免疫チェックポイント阻害治療による抗腫瘍効果および免疫関連副作用を同一個体で解析することが可能なマウスモデルを確立した。これにより癌免疫応答および自己免疫応答の連関を検討することが容易となり、今後免疫チェックポイント阻害の効果を最大化するための癌治療戦略の創出を目的とした基礎研究に有用な病態モデルであると考えられる。