IL33-induced lipid droplet formation in mature low-density neutrophils drives colorectal cancer liver metastasis.

ABSTRACT: The microenvironment of distant organs affects the colonization and growth of disseminated tumor cells. It remains unclear how tumor-associated neutrophils are influenced by the microenvironment of distant organs. Here, we demonstrate that mature low-density neutrophils in colorectal cancer patients abnormally accumulate neutral lipids and induce the reactivation of dormant tumor cells, a process regulated by hepatic stellate cells. Mechanistically, activated hepatic stellate cells increased DGAT1/2-dependent lipid droplet synthesis in low-density neutrophils through the secretion of IL33, thereby maintaining the survival and immunosuppressive function of these neutrophils. The uptake of lipids from lipid-laden low-density neutrophils drives dormant tumor cell reactivation through the pote

SUBMITTER: Zhang Y 

PROVIDER: S-EPMC12660769 | biostudies-literature | 2025 Dec

REPOSITORIES: biostudies-literature