配分額 *注記 |
4,680千円 (直接経費: 3,600千円、間接経費: 1,080千円)
2023年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
2022年度: 2,080千円 (直接経費: 1,600千円、間接経費: 480千円)
2021年度: 1,300千円 (直接経費: 1,000千円、間接経費: 300千円)
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研究実績の概要 |
Backgrounds: Immune cells with somatic mutations (IMsm) are infiltrated into cancer tissues in cancer patients with clonal hematopoiesis (CH). The roles of IMsm may vary depending on cancer types. Aim: To examine the roles of IMsm in colon cancer metastasis. Methods: We transplanted colon cancer organoid cells into spleens of various Tet2 conditional knockout mice: VAV1Cre (Tet2 gene deletion in all hematopoietic cells), LysMCre (myeloid), CD19Cre (B), and CD4Cre (T). Livers were collected 30 days after transplantation. Liver metastasis tumor burden (LMTB) was defined by numbers of tumor foci, manually counted in 10 slides. Sorted CD4+, CD8+, CD11b+, and CD19+ cells were subjected to whole transcriptome analysis (WTA), respectively. Results: LMTB of VAV1Cre and CD4Cre were lower than those of control (VAV vs cont, 55 vs 77 foci/1000 mm2; p<0.05; CD4 vs cont, 55 vs 86 foci/1000mm2; p<0.05), while that of CD19Cre and LysMCre were comparable. Differentially expressed gene (DEG) analysis for WTA showed that Pdcd1, Tim3, Tigit, and Lag3, encoding inhibitory receptors were repressed in CD8+ cells sorted from VAV1Cre and CD4Cre livers comparing to those of control. Immunofluorescence staining showed that PDCD1+TIM3+CD8+ cells were decreased in VAV1Cre livers comparing to control. We also found that transcription factor X that regulates the expression of the inhibitory receptors was highly expressed in tumor infiltrated-CD8 cells of control mice compared those of VAV1Cre and CD4Cre mice.
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