| First Author | Nguyen YTM | Year | 2021 |
| Journal | Cancer Sci | Volume | 112 |
| Issue | 12 | Pages | 4931-4943 |
| PubMed ID | 34657351 | Mgi Jnum | J:330934 |
| Mgi Id | MGI:6836025 | Doi | 10.1111/cas.15165 |
| Citation | Nguyen YTM, et al. (2021) Tet2 deficiency in immune cells exacerbates tumor progression by increasing angiogenesis in a lung cancer model. Cancer Sci 112(12):4931-4943 |
| abstractText | Immune cells harboring somatic mutations reportedly infiltrate cancer tissues in patients with solid cancers and accompanying clonal hematopoiesis. Loss-of-function TET2 mutations are frequently observed in clonal hematopoiesis in solid cancers. Here, using a mouse lung cancer model, we evaluated the activity of Tet2-deficient immune cells in tumor tissues. Myeloid-specific Tet2 deficiency enhanced tumor growth in mice relative to that seen in controls. Single-cell sequencing analysis of immune cells infiltrating tumors showed relatively high expression of S100a8/S100a9 in Tet2-deficient myeloid subclusters. In turn, treatment with S100a8/S100a9 promoted Vegfa production by cancer cells, leading to a marked increase in the tumor vasculature in Tet2-deficient mice relative to controls. Finally, treatment of Tet2-deficient mice with an antibody against Emmprin, a known S100a8/S100a9 receptor, suppressed tumor growth. These data suggest that immune cells derived from TET2-mutated clonal hematopoiesis exacerbate lung cancer progression by promoting tumor angiogenesis and may provide a novel therapeutic target for lung cancer patients with TET2-mutated clonal hematopoiesis. |
