Novel immunoediting mechanisms via somatic mutations

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K22574
• Research Category: Grant-in-Aid for Challenging Research (Exploratory)
• Allocation Type: Multi-year Fund
• Review Section: Medium-sized Section 50:Oncology and related fields
• Research Institution: Chiba Cancer Center (Research Institute)
• Principal Investigator: Togashi Yosuke 千葉県がんセンター(研究所), がん治療開発グループ 細胞治療開発研究部, 部長代理 (80758326)
• Project Period (FY): 2019-06-28 – 2021-03-31
• Keywords: がん免疫編集 / 腫瘍免疫 / ネオ抗原

Outline of Final Research Achievements

Cancer cells with high tumor mutation burden (TMB) can have a more malignant phenotype, but strong antitumor immunity can be also induced by high TMB. Here, we have found that a fraction of patients has non-inflamed tumor microenvironment despite high TMB due to some signaling pathways related to the malignant phenotype and we could validate several pathways using mouse models. From these findings, novel immunoediting mechanisms via somatic mutations is proposed, and we should consider not only just simple TMB but also the quality.

Free Research Field

腫瘍微小環境学

Academic Significance and Societal Importance of the Research Achievements

従来の「がん免疫編集」に加えて、がんが悪性度に関わるようなシグナルを巧みに利用して免疫系から逃れているという新たながん免疫編集を明らかにした。そのような悪性度に関わるシグナルもいくつか同定し、それらはがん免疫療法の治療標的になる可能性があり、今後のバイオマーカーや併用療法としての新たな治療開発に繋がるデータである。