RRC ID 81675
Author 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.
Title IL36G-producing neutrophil-like monocytes promote cachexia in cancer.
Journal 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.
Volume 15(1)
Pages 7662
Published 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
Resource
Human and Animal Cells C2C12(RCB0987) B16 melanoma(RCB1283)