Search for TPO for immunotherapy using immunosuppressive neutrophils and cancer immune-promoting neutrophils

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K09554
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56030:Urology-related
• Research Institution: Yamagata University
• Principal Investigator: Takeda Yuji 山形大学, 医学部, 准教授 (90302299)
• Co-Investigator(Kenkyū-buntansha): 加藤 智幸 山形大学, 医学部, 非常勤講師 (40396560) ; 斉藤 真一 山形大学, 医学部, 助教 (90536674) ; 奈良 英利 石巻専修大学, 理工学部, 准教授 (00375338) ; 浅尾 裕信 山形大学, 医学部, 教授 (80250744)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 腎癌 / 免疫チェックポイント阻害剤 / 好中球 / 炎症 / 抗腫瘍活性 / 免疫抑制活性 / MDSCs

Outline of Final Research Achievements

Various combination treatment with immune-checkpoint inhibitors (ICI) therapy are being tried to improve the clinical outcome to tumor treatment. Since inflammation-induced myeloid-derived suppressor cells (MDSCs) suppress tumor immunity, regulation of MDSCs is a promising novel combination therapy. However, since the classification of MDSC has not been determined, it has not been applied clinically. In this study, we estimated the state of myeloid cells, including MDSC, and examined their relationship with the clinical efficacy of ICI treatment. We found that elevated CD16 and LAP-1 expression was associated with poor response to ICI therapy, and GPI-80 expression on neutrophils just prior to initiation of ICI therapy was significantly higher in complete responders.

Free Research Field

免疫学

Academic Significance and Societal Importance of the Research Achievements

本研究では、免疫抑制・促進のモザイクな細胞集団の骨髄系細胞（主に好中球）の出現パターンと、免疫チェックポイント阻害治療の効果との関係を明らかにした。この結果は、治療の有効率を上げ、副作用を減らす、最適な免疫治療のTPO [時(time)・所(place)・場合(occasion)]の基盤的知見となる。この知見は、がん免疫治療・自己免疫疾患治療・臓器移植など、様々な治療や予防に応用できると考えている。最終的には、免疫治療を受ける患者の負担軽減や、医療費削減効果をもたらす事ができると期待している。