Evidence map›Paper›PMID 41214328›Full record

ArticleCellular & molecular immunology2025

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

Yuchen Zhang, Suyue Yu, Dina Yeernuer, Wangyi Liu, Zhuoqing Xu, Wenqing Feng, Zeping Lv, Xuanhao Liu, Peiqi Tan, Minhua Zheng and 3 more

Abstract read
In one paragraph

Article in Cellular & molecular immunology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.

0numbers the graph read from it
0cells of the map it votes in
11citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

11 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Article
  5. Review
  6. Review
  7. Review
  8. Review
  9. Review
  10. Review
  11. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

13 authors.

Yuchen Zhang *Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Suyue Yu *Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Dina Yeernuer *Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wangyi Liu *Department of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zhuoqing XuDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Wenqing FengDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Zeping LvDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Xuanhao LiuDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Peiqi TanDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Minhua ZhengDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
Yaping ZongDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. angela_zyp@126.com.
Aiguo LuDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. luaiguo1965@163.com.
Jingkun ZhaoDepartment of General Surgery, Ruijin Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China. zjk12569@rjh.com.cn.

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81802326National Natural Science Foundation of China (National Science Foundation of China) 82473026
6 · The paper itself

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 potentiation of β-oxidation and the stimulation of protumorigenic eicosanoid synthesis. In mouse models, targeting IL33 blocked neutrophil lipid synthesis, decreased the colonization of colorectal cancer cells in the liver, and enhanced the efficacy of immunotherapy. Overall, our study revealed that lipid accumulation in mature low-density neutrophils regulates the growth of dormant tumor cells and antitumor immunity to facilitate colorectal cancer liver metastasis. Targeting IL33 could be a promising therapeutic approach for colorectal cancer liver metastases.

Indexed as

Colorectal NeoplasmsInterleukin-33Lipid DropletsLiver NeoplasmsNeutrophilsAdultAgedAged, 80 and overAnimalsDiacylglycerol O-AcyltransferaseFemaleHCT116 CellsHepatic Stellate CellsHumansImmunotherapyLipid MetabolismDiacylglycerol O-AcyltransferaseInterleukin-33PPAR gammaTOR Serine-Threonine KinasesTriglyceridescolorectal cancerlipid dropletsliver metastasismature low-density neutrophilsmetabolic reprogramming

Identifiers

PMID41214328
PMCPMC12660769

What Socratic holds

Textmetadata
LicenceCC BY
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.