2019 Fiscal Year Final Research Report

Establishment of separation method for immunosuppressive neutrophils and antitumor neutrophils in renal cancer and bladder cancer

Research Project

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Project/Area Number	17K11122
Research Category	Grant-in-Aid for Scientific Research (C)
Allocation Type	Multi-year Fund
Section	一般
Research Field	Urology
Research Institution	Yamagata University
Principal Investigator	Takeda Yuji 山形大学, 医学部, 准教授 (90302299)
Co-Investigator(Kenkyū-buntansha)	奈良英利石巻専修大学, 理工学部, 准教授 (00375338) 黒田悠太山形大学, 医学部, 助教 (00594326) 加藤智幸山形大学, 医学部, 准教授 (40396560) 土谷順彦山形大学, 医学部, 教授 (70282176) 浅尾裕信山形大学, 医学部, 教授 (80250744)
Project Period (FY)	2017-04-01 – 2020-03-31
Keywords	膀胱がん / 炎症 / BCG / 好中球 / 抗腫瘍活性 / MDSCs
Outline of Final Research Achievements	In renal cancer patients, immunosuppressive neutrophils called myeloid-derived suppressor cells (MDSCs) appear due to cancerous chronic inflammation. On the other hand, intravesical BCG instillation therapy for non-muscle invasive bladder cancer induces strong inflammation and provides a strong anti-tumor immune response. In this study, we investigated the BCG-induced inflammatory response and tried to find the indicators of neutrophil-like cells associated with anti-tumor immune response. As a result, no increase in MDSCs was observed during the BCG treatment. While, the expression of HLA-II and CXCL10 were increased in neutrophil-like cells in urine. Since it is known that HLA-II and CXCL10 induce activation of the adaptive immune system, it was considered that they could be useful indicators of anti-tumor neutrophil-like cells.
Free Research Field	免疫学
Academic Significance and Societal Importance of the Research Achievements	本研究により、免疫抑制型好中球と抗腫瘍型好中球の指標を得ることが出来た。これは、がん治療の予後予測や適切な治療時期の判断に使用できる可能性がある。具体的には、免疫抑制型好中球が少ない時期を狙って、免疫チェックポイント阻害剤治療を開始する治療方法や、過剰な炎症により免疫抑制型好中球が増加してきた時期には、治療を中断し、がん免疫応答の回復を待つなど、様々ながん治療の最適化を実現できるかもしれない。また、BCGを用いて、体外および体内で『抗腫瘍型好中球』を補完・誘導する免疫治療法に発展できる可能性もある。これらが実現すれば、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と予想できる。