Immunological monitoring of the management of the immune-related adverse events

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08785
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54020:Connective tissue disease and allergy-related
• Research Institution: St. Marianna University School of Medicine
• Principal Investigator: KAWAHATA Kimito 聖マリアンナ医科大学, 医学部, 教授 (70334406)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: 免疫関連有害事象 / PD-1 / 免疫チェックポイント阻害療法

Outline of Final Research Achievements

Tph cells (CD200 + CXCR5-PD-1 + CD4 + T cells) and autoimmune-related B cells (CD21lowCD11c+T-bet+B cells) in peripheral blood mononuclear cells (62 patients, 22 of whom had immune-related adverse events) were identified using FACS. These cells were not significantly elevated after immune checkpoint inhibition therapy or immune-related adverse events. However, some cases were found in which the proportion of these autoimmune-related lymphocytes were remarkably elevated. In patients who developed immune-related adverse events of myositis during pembrolizumab administration, the percentage of autoimmune-related B cells among CD19-positive cells was 3.5% before onset, but after onset (10 days after onset of immune-related adverse events) was 10.5%. We also detected Tph cells with cytotoxic molecules in many cases.

Free Research Field

リウマチ学、膠原病学

Academic Significance and Societal Importance of the Research Achievements

この研究はがん免疫治療副作用マネージメントへの免疫モニタリングの導入であり、従来の副作用マネージメントとは全く発想が異なる。疾患が生じてから、症候や検査値異常をもとにそれを発見しマネージメントを開始するのではなく、本治療法により増大する自己免疫関連T細胞およびB細胞の出現を検出する方法であり、独自性、汎用性が高い。すなわち早期発見とともにがん免疫療法再開の判断などに役立つ。更に、本研究は、薬剤投与からT細胞の活性化、B細胞への影響までを通して明らかにできる点で、ヒト免疫学、特に自己免疫疾患の病態理解への貢献が期待できる。