2021 Fiscal Year Final Research Report

Expression and function analysis of MDSC as a predictive factor of novel immunotherapy with GPI-80

Research Project

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Project/Area Number	19K09704
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	Kato Tomoyuki 山形大学, 医学部, 准教授 (40396560)
Co-Investigator(Kenkyū-buntansha)	武田裕司山形大学, 医学部, 准教授 (90302299) 内藤整山形大学, 医学部, 講師 (00431643) 黒田悠太山形大学, 医学部, その他 (00594326) 土谷順彦山形大学, 医学部, 教授 (70282176)
Project Period (FY)	2019-04-01 – 2022-03-31
Keywords	MDSCs / 腎癌 / GPI-80
Outline of Final Research Achievements	In chronic inflammatory conditions such as renal cancer, MDSCs appear and suppress the cancer immune response. We have previously established a method for analyzing MDSCs in the peripheral blood of patients with renal cancer using the expression level and coefficient variation of GPI-80, combining with myeloid-differentiation markers. We investigated changes in the number and function of MDSCs using peripheral blood before and during cancer therapies. The increasing MDSCs indexes (CD16 and LAP-1 expression level) were associated with poor response to each cancer therapy. In cases of immune-related side effects, GPI-80 coefficient variation, which is other MDSCs indicators, was reduced. In the case of complete response, neutrophils with increased GPI-80 expression level were significantly observed before the therapie. Since GPI-80 was involved in the activation of NF-κB, it is possible that it is involved in neutrophil function that enhances the cancer immune response.
Free Research Field	泌尿器科
Academic Significance and Societal Importance of the Research Achievements	本研究で、免疫チェックポイント阻害薬を用いた薬物療法の治療前および治療初期の骨髄系細胞の変動が、抗腫瘍効果と免疫関連有害事象に関連していることが明らかとなった。完全奏効症例では治療前に好中球のGPI-80発現量が上昇しており、GPI-80発現量増加の時期を狙って免疫チェックポイント阻害剤を投与することで、より高い抗腫瘍効果が得られる可能性がある。さらに、薬剤投与やや慢性炎症により、CD16・LAP-1発現量上昇単球が増加してきた場合、治療を一時中断して免疫応答の回復を待つなど、癌治療の最適化にも寄与しうる。また、『GPI-80高発現型好中球』を補完・誘導する免疫治療法に発展する可能性もある。