๐ค Authors: Yoshihiro Hayashi, Yasushige Kamimura-Aoyagi, Sayuri Nishikawa, Rena Noka, Rika Iwata, Asami Iwabuchi, Yushin Watanabe, Natsumi Matsunuma, Kanako Yuki, Hiroki Kobayashi, Yuka Harada, Hironori Harada
IL36G-producing neutrophil-like monocytes promote cachexia in cancer.
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 36โgamma (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.
