Evidence map›Paper›PMID 38951890›Full record

ArticleJournal of biomedical science2024

Cholestasis-induced phenotypic transformation of neutrophils contributes to immune escape of colorectal cancer liver metastasis.

Li Sun, Nanyan Yang, Zhihong Liu, Xiandong Ye, Mengting Cheng, Lingjun Deng, Junhao Zhang, Jingjing Wu, Min Shi, Wangjun Liao

Abstract read
In one paragraph

Article in Journal of biomedical science, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing 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

8 citing papers in PubMed.

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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

10 authors.

Li Sun *Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Nanyan Yang *Department of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Zhihong LiuDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Xiandong YeDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Mengting ChengDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Lingjun DengDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Junhao ZhangDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Jingjing WuDepartment of Thoracic Medical Oncology, Cancer Hospital of the University of Chinese Academy of Sciences, Zhejiang Cancer Hospital, Hangzhou, Zhejiang, China.
Min ShiDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China.
Wangjun LiaoDepartment of Oncology, Nanfang Hospital, Southern Medical University, Guangzhou, 510515, Guangdong, China. nfyyliaowj@163.com.ORCID http://orcid.org/0000-0002-1364-8442

Funding

National Natural Science Foundation of China 81972292National Natural Science Foundation of China 82272635Natural Science Foundation of Beijing Municipality 7242139Scientific and Technology Planning Project of Guangzhou City 202102020076
6 · The paper itself

Abstract

backgroundCholestasis is a common yet severe complication that occurs during the advancement of liver metastasis. However, how cholestasis impacts the development, treatment, and tumor microenvironment (TME) of liver metastasis remains to be elucidated.

methodsExtrahepatic and intrahepatic cholestatic mouse models with liver metastasis were established to detect the differential expression levels of genes, infiltration of immune cells and change in bile acid-associated metabolites by using RNA-Sequencing, flowcytometry, and liquid chromatography and mass spectrometry. Western blot was applied to neutrophils under the stimulation of primary bile acids (BAs) in vitro to study the mechanism of phenotypic alteration. In vitro coculture of BA-treated neutrophils with CD8

resultsCompared to non-cholestatic mice, the progression of liver metastasis of cholestatic mice was significantly accelerated, which was associated with increased neutrophil infiltration and T-cell exclusion. Both neutrophils and T cells expressed higher immunosuppressive markers in the cholestatic mouse model, further indicating that an immunosuppressive tumor microenvironment was induced during cholestasis. Although neutrophils deletion via anti-Ly6G antibody partially hindered liver metastasis progression, it reduced the overall survival of mice. Tauro-β-muricholic acid (Tβ-MCA) and Glycocholic acid (GCA), the two most abundant cholestasis-associated primary BAs, remarkably promoted the expression of Arg1 and iNOS on neutrophils via p38 MAPK signaling pathway. In addition, BAs-pretreated neutrophils significantly suppressed the activation and cytotoxic effects of CD8

conclusionsOur study reveals the TME of cholestasis-associated liver metastasis and proposes a new strategy for such patients by targeting bile acid anabolism.

Indexed as

CholestasisColorectal NeoplasmsLiver NeoplasmsNeutrophilsAnimalsDisease Models, AnimalHumansMaleMiceMice, Inbred C57BLTumor MicroenvironmentBile acidsCholestasisColorectal cancer liver metastasisNeutrophilTumor microenvironment

Identifiers

PMID38951890
PMCPMC11218316

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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 OpenQuestion graph.