論文 - 詳細
| RRC ID | 81675 |
|---|---|
| 著者 | Hayashi Y, Kamimura-Aoyagi Y, Nishikawa S, Noka R, Iwata R, Iwabuchi A, Watanabe Y, Matsunuma N, Yuki K, Kobayashi H, Harada Y, Harada H. |
| タイトル | IL36G-producing neutrophil-like monocytes promote cachexia in cancer. |
| ジャーナル | Nat Commun |
| Abstract |
Most patients with advanced cancer develop cachexia, a multifactorial syndrome characterized by progressive skeletal muscle wasting. Despite its catastrophic impact on survival, the critical mediators responsible for cancer cachexia development remain poorly defined. Here, we show that a distinct subset of neutrophil-like monocytes, which we term cachexia-inducible monocytes (CiMs), emerges in the advanced cancer milieu and promotes skeletal muscle loss. Unbiased transcriptome analysis reveals that interleukin 36 gamma (IL36G)-producing CD38+ CiMs are induced in chronic monocytic blood cancer characterized by prominent cachexia. Notably, the emergence of CiMs and the activation of CiM-related gene signatures in monocytes are confirmed in various advanced solid cancers. Stimuli of toll-like receptor 4 signaling are responsible for the induction of CiMs. Genetic inhibition of IL36G-mediated signaling attenuates skeletal muscle loss and rescues cachexia phenotypes in advanced cancer models. These findings indicate that the IL36G-producing subset of neutrophil-like monocytes could be a potential therapeutic target in cancer cachexia. |
| 巻・号 | 15(1) |
| ページ | 7662 |
| 公開日 | 2024-9-12 |
| DOI | 10.1038/s41467-024-51873-x |
| PII | 10.1038/s41467-024-51873-x |
| PMID | 39266531 |
| PMC | PMC11393454 |
| MeSH | Animals Cachexia* / etiology Cachexia* / metabolism Cell Line, Tumor Female Gene Expression Profiling Humans Interleukins / genetics Interleukins / metabolism Male Mice Mice, Inbred C57BL Monocytes* / immunology Monocytes* / metabolism Muscle, Skeletal* / metabolism Muscle, Skeletal* / pathology Neoplasms* / complications Neoplasms* / immunology Neoplasms* / metabolism Neutrophils* / metabolism Signal Transduction Toll-Like Receptor 4 / genetics Toll-Like Receptor 4 / metabolism |
| IF | 12.121 |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | X(Twitter) |
| 各媒体での言及数の合計 | 15 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | C2C12(RCB0987) B16 melanoma(RCB1283) |