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) |