Evidence map›Paper›PMID 41387425›Full record

ArticleNature communications2025

Liver-specific paraoxonase-1 alleviates regulatory T cell-driven immunosuppression via metabolic reprogramming in hepatocellular carcinoma.

Zhou Lu, Huanchen Shi, Rongshan Gao, Chengjie Zhong, Wei Zhang, Jian Zhu, Jianhang Huang, Ronghua Liu, Yun Xing, Yiwei Chu and 8 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Nature communications, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.

0numbers the graph read from it
0cells of the map it votes in
1citing 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

1 citing paper in PubMed.

  1. Article
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

18 authors.

Zhou Lu *Institute of Clinical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China. lu.zhou1@zs-hospital.sh.cn.ORCID http://orcid.org/0000-0002-7689-0033
Huanchen Shi *Department of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Rongshan Gao *Department of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Chengjie ZhongDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Wei ZhangInstitute of Clinical Sciences, Zhongshan Hospital, Fudan University, Shanghai, China.
Jian ZhuDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Jianhang HuangDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Ronghua LiuDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Yun XingDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.
Yiwei ChuDepartment of Immunology, School of Basic Medical Sciences, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-5035-1111
Haixiang SunDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Guoming ShiDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0003-3817-9117
Aiwu KeDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Jian ZhouDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0002-2118-1117
Jiabin CaiDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.
Jia FanDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China.ORCID http://orcid.org/0000-0001-5158-629X
Pingting GaoEndoscopy Center and Endoscopy Research Institute, Fudan University, Shanghai, China. gao.pingting@zs-hospital.sh.cn.
Cheng HuangDepartment of hepatobiliary Surgery and liver Transplantation, Liver Cancer Institute and Zhongshan Hospital, Fudan University, Shanghai, China. huang.cheng@zs-hospital.sh.cn.ORCID http://orcid.org/0000-0003-1348-6268

Funding

National Natural Science Foundation of China (National Science Foundation of China) 81572298,81871929,82072667,82272703,82473201
6 · The paper itself

Abstract

Paraoxonase-1 (PON1) is specifically expressed in the liver and has crucial effects on various liver diseases. The functions and underlying mechanisms of PON1 in hepatocellular carcinoma (HCC) remain unclear. Here, we demonstrate that PON1 serves as a metabolic regulator to counteract regulatory T (Treg) cell-mediated immunosuppression, thereby suppressing HCC progression. Mechanistically, PON1 promotes Von Hippel-Lindau protein (VHL)-mediated ubiquitination and degradation of hypoxia-inducible factor alpha (HIF-1α), leading to attenuated lactic acid production and limited Treg cell accumulation in the HCC microenvironment. In clinical settings, higher PON1 expression is correlated with a better prognosis in patients with HCC. Recombinant PON1 protein (rPON1) effectively impeded tumor growth. Furthermore, enhancing Pon1 expression with quercetin sensitized HCC to anti-programmed death-1(PD-1) therapy in murine HCC. Our findings elucidate a role of PON1 in orchestrating lactic acid production to relieve immunosuppression and suppress HCC, paving the way for targeting PON1 as a therapeutic strategy.

Indexed as

AryldialkylphosphataseCarcinoma, HepatocellularLiver NeoplasmsT-Lymphocytes, RegulatoryAnimalsCell Line, TumorFemaleHumansHypoxia-Inducible Factor 1, alpha SubunitImmune ToleranceLactic AcidLiverMaleMetabolic ReprogrammingMiceMice, Inbred C57BLAryldialkylphosphataseHIF1A protein, humanHypoxia-Inducible Factor 1, alpha SubunitLactic AcidPON1 protein, human

Identifiers

PMID41387425
PMCPMC12701056

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
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.