Evidence map›Paper›PMID 39733452›Full record

ArticleAdvanced science (Weinheim, Baden-Wurttemberg, Germany)2025

Targeting Deltex E3 Ubiquitin Ligase 2 Inhibits Tumor-associated Neutrophils and Sensitizes Hepatocellular Carcinoma Cells to Immunotherapy.

Xiaoling Wu, Jiafeng Chen, Yiran Chen, Shushu Song, Yuan Fang, Shengwei Mao, Jun Gao, Guiqi Zhu, Weifeng Qu, Qianfu Zhao and 12 more

Abstract read
In one paragraph

Article in Advanced science (Weinheim, Baden-Wurttemberg, Germany), 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
13citing papers in PubMed, 1 pooled it
–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

13 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Article
  3. Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Review
  9. Article
  10. Ubiquitination in hepatocellular carcinoma immunity.Journal of translational medicine · 2025
    Review
  11. Article
  12. Article
  13. 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

22 authors.

Xiaoling WuDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jiafeng ChenDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yiran ChenKey Laboratory of Carcinogenesis and Cancer Invasion of Ministry of Education, Shanghai, 200032, China.
Shushu SongDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Yuan FangDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Shengwei MaoDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jun GaoDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Guiqi ZhuDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Weifeng QuDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Qianfu ZhaoDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Rui YangDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Zhiqi GuanDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Tianhao ChuDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yichao BuDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yi WangDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Fangyu ChenDepartment of Radiation Oncology, Zhongshan Hospital Affiliated to Fudan University, Shanghai, 200032, China.
Jian ZhouDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Jia FanDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Zheng TangDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Weiren LiuDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.
Yuanyuan RuanDepartment of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Yinghong ShiDepartment of Liver Surgery and Transplantation, Zhongshan Hospital, Fudan University, Shanghai, 200032, China.ORCID https://orcid.org/0000-0002-1833-8988

Funding

CIFMS 2019-I2M-5-058Clinical Research Plan of SHDC SHDC2020CR5007National Key R&D Program of China 2018YFC1312100National Key R&D Program of China 2020YFE0202200National Natural Science Foundation of China 82003084National Natural Science Foundation of China 82073217National Natural Science Foundation of China 82073218National Natural Science Foundation of China 82073245National Natural Science Foundation of China 82122051National Natural Science Foundation of China 82273386National Natural Science Foundation of China 82273387National Natural Science Foundation of China 82403408Outstanding Resident Clinical Postdoctoral Program of Zhongshan Hospital Affiliated to Fudan University 2023ZYYS-011Science and Technology Major Project 2018SHZDZX05Shanghai Municipal Health Commission 202040221
6 · The paper itself

Abstract

Several E3 ligases have been found to affect the immune microenvironment of hepatocellular carcinoma (HCC) and lead to the resistance of immunotherapy. In this study, genes of E3 ligases are screened based on The Cancer Genome Atlas (TCGA) dataset. Through cytometry by time of flight (CyTOF), flow cytometry, and further experiments, Deltex E3 ubiquitin ligase 2 (DTX2) in HCC cells is identified to promote the infiltration and polarization of tumor-associated neutrophils (TANs) with a protumor phenotype, thus attenuating the infiltration and cytotoxicity of CD8+ T cells partially through C-X-C motif chemokine 2 (CXCL2) and C-X-C motif chemokine 6 (CXCL6). Mechanistically, DTX2 can interact with histone H2B and promote its monoubiquitination at lysine120 (H2BK120ub1), thereby increasing CXCL2 and CXCL6 transcription through histone epigenetic regulation. Different tumor models in vivo demonstrated that DTX2 inhibitor treatment inhibited tumor growth and sensitized HCC cells to the therapeutic effects of programmed cell death protein 1 (PD-1) antibody. In summary, this study identifies DTX2 as a potential target for HCC immunotherapy.

Indexed as

Carcinoma, HepatocellularImmunotherapyLiver NeoplasmsNeutrophilsUbiquitin-Protein LigasesAnimalsCell Line, TumorHumansMiceTumor MicroenvironmentUbiquitin-Protein Ligasesdeltex E3 ubiquitin ligase 2DTX2 inhibitorhepatocellular carcinomatumor‐associated neutrophils

Identifiers

PMID39733452
PMCPMC11831464

What OpenQuestion holds

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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 OpenQuestion graph.