2023 Fiscal Year Final Research Report
Studying the role of clonal hematopoiesis in mouse solid tumors using a native-tissue relevant context model
| Project/Area Number |
21K15478
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| Research Category |
Grant-in-Aid for Early-Career Scientists
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| Allocation Type | Multi-year Fund |
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| Review Section |
Basic Section 50010:Tumor biology-related
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| Research Institution | University of Tsukuba |
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Principal Investigator |
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| Project Period (FY) |
2021-04-01 – 2024-03-31
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| Keywords | Clonal hematopoiesis / Colorectal cancer / TET2 |
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| Outline of Final Research Achievements |
Immune cells with somatic mutations (IMsm) are infiltrated into tumor tissues in cancer patients with clonal hematopoiesis (CH). To examine the roles of IMsm in colorectal liver metastasis (CLM), colon cancer organoid cells (CCOC) were transplanted into spleens of various Tet2 conditional knockout mice: VAVCre (Tet2 deletion in all blood cells), LysMCre (myeloid), CD19Cre (B), and CD4Cre (T). We found that CML tumor burden of VAVCre and CD4Cre were lower than those of control. Differentially expressed gene analysis for WTA and immunofluorescence staining showed that PDCD1, TIM3, TIGIT, and LAG3, encoding inhibitory receptors were repressed in CD8+ cells sorted from VAVCre and CD4Cre livers comparing to control. In conclusion, deficiency of Tet2 in hematopoietic cells led to decrease of exhausted CD8+ T cells and suppressed CLM.
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| Free Research Field |
Cancer immunity
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| Academic Significance and Societal Importance of the Research Achievements |
We clarified the roles of clonal hematopoiesis in a colorectal cancer (CRC) liver metastasis model which is native-relevant. Our findings may bring attention about CH in the prognosis and treatment of CRC in the era of precision medicine.
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