Elucidation of the molecular mechanisms of crosstalk between inflammatory cells with somatic mutations and cancer cells

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K21535
• 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: University of Tsukuba
• Principal Investigator: Sakata-Yanagimoto Mamiko (柳元麻実子) 筑波大学, 医学医療系, 教授 (80451805)
• Co-Investigator(Kenkyū-buntansha): 野口 雅之 筑波大学, 医学医療系, 教授 (00198582) ; 服部 圭一朗 筑波大学, 附属病院, 病院講師 (10832024)
• Project Period (FY): 2020-07-30 – 2022-03-31
• Keywords: メラノーマ / がん微小環境 / クローン造血

Outline of Final Research Achievements

Applicants believe that genomic abnormalities in the cancer cells themselves affect the microenvironment, and the interaction between mutated cancer cells and mutated inflammatory cells derived from "cloned hematopoiesis" creates a unique cancer microenvironment. I have been conducting research with the hypothesis that it will be formed. In previous studies, Tet2-deficient mice were used in the hematopoietic line as a representative of "clonal hematopoiesis", and melanoma cells with two types of genomic abnormalities and two types of melanoma cells with additional genomic abnormalities were added. When melanoma cells having two types of genomic abnormalities were transplanted, the formation of tumor cells was promoted, but no significant difference was observed when four types of melanoma cells were transplanted.

Free Research Field

がん微小環境

Academic Significance and Societal Importance of the Research Achievements

健常にみえる場合であっても、造血システムは加齢と共に体細胞変異を獲得したクローン造血に置き換わることが報告された。固形がん患者では、健常な高齢者に比較して、「クローン造血」の頻度が高い。「クローン造血」のある場合には、がん組織に「クローン造血」から分化した体細胞変異のある炎症細胞が浸潤して、がん微小環境を形成する可能性と考えられ、がん微小環境に関する理解を大幅に変える研究分野に発展すると思われる。