Elucidation of pathogenesis of cytokine release syndrome by cancer immunotherapy in normal immunity mice and development of new treatment

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K07426
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto Prefectural University of Medicine
• Principal Investigator: Okayama Tetsuya 京都府立医科大学, 医学(系)研究科(研究院), 助教 (30636535)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: サイトカイン放出症候群

Outline of Final Research Achievements

Although cancer immunotherapy has increased therapeutic efficacy, it also produces powerful side effects, the most notable of which is called cytokine release syndrome (CRS), which is often fatal. In order to understand the pathology, we happened to discover an animal model using normal immune mice, not immunodeficient mice. As a detailed study, various organs (brain, heart, lung, liver, kidney, spleen) excised until death after two doses of NK cells were examined by HE staining and other staining. Since there was no marked inflammatory cell infiltration or injury in each organ, 31 types of cytokines were measured and analyzed in the serum collected at the same time. As a result, it was suggested that CCL1, CCL7, and CCL24 might play a central role.

Free Research Field

がん免疫療法

Academic Significance and Societal Importance of the Research Achievements

がん治療に革新をもたらした免疫チェックポイント阻害剤は、副作用も強力である。その最たるものは、サイトカイン放出症候群（CRS）であり、致死的となり得る。その病態解明や制御は喫緊の課題であり、我々は世界初の免役不全マウスを用いない自然免疫下での動物実験モデルを確立した。このモデルを用い、網羅的なサイトカインの検索にて、CCL1、CCL7、CCL24が中心的である可能性が示唆された。
今後これらの新たな知見からCRSの病態解明・制御に向けた検討を行うことは、がん免疫療法のみならず、CRSは新型コロナウイルス感染症でも注目されたものであり、学術的な意義のみならず、社会的意義も大きいものと思われる。