Evidence map›Paper›PMID 41876134›Full record

ArticleJournal for immunotherapy of cancer2026

Targeted inhibition of Nrf2 potentiates antitumor immunity and enhances the efficacy of immunotherapy in hepatocellular carcinoma.

Yan Zhu, Maoxuan Liu, Xiaokai Fan, Yingying Xu, Xueling Diao, Jiacheng Bi, Xiaochun Wan, Yehuda G Assaraf, Hang Fai Kwok, Liang Chen

Abstract read
In one paragraph

Article in Journal for immunotherapy of cancer, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing 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

2 citing papers in PubMed.

  1. Article
  2. 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

10 authors.

Yan Zhu *Molecular Cancer Research Center, School of Medicine, Sun Yat-sen University - Shenzhen Campus, Shenzhen, Guangdong, China.ORCID http://orcid.org/0000-0002-5730-6479
Maoxuan Liu *Shenzhen Laboratory of Tumor Cell Biology, Institute of Biomedicine and Biotechnology, Shenzhen Institute of Advanced Technology Chinese Academy of Sciences, Shenzhen, Guangdong, China.ORCID http://orcid.org/0000-0002-0953-9673
Xiaokai FanMolecular Cancer Research Center, School of Medicine, Sun Yat-sen University - Shenzhen Campus, Shenzhen, Guangdong, China.
Yingying XuMolecular Cancer Research Center, School of Medicine, Sun Yat-sen University - Shenzhen Campus, Shenzhen, Guangdong, China.
Xueling DiaoMolecular Cancer Research Center, School of Medicine, Sun Yat-sen University - Shenzhen Campus, Shenzhen, Guangdong, China.
Jiacheng BiShenzhen Institute of Advanced Technology Chinese Academy of Sciences, Shenzhen, Guangdong, China.ORCID http://orcid.org/0000-0001-5646-0119
Xiaochun WanShenzhen Institute of Advanced Technology Chinese Academy of Sciences, Shenzhen, Guangdong, China.
Yehuda G AssarafThe Fred Wyszkowski Cancer Research Laboratory, Faculty of Biology, Technion Israel Institute of Technology, Haifa, Israel.
Hang Fai KwokCancer Centre, Department of Biomedical Sciences, Faculty of Health Sciences and MoE Frontiers Science Centre for Precision Oncology, University of Macau, Macau, China hfkwok@um.edu.mo chenliang37@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-6349-4517
Liang ChenMolecular Cancer Research Center, School of Medicine, Sun Yat-sen University - Shenzhen Campus, Shenzhen, Guangdong, China hfkwok@um.edu.mo chenliang37@mail.sysu.edu.cn.ORCID http://orcid.org/0000-0002-4875-5811

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundImmune checkpoint inhibitors (ICIs) and chimeric antigen receptor T-cell (CAR-T) immunotherapies have revolutionized the treatment of hepatocellular carcinoma (HCC). However, the frequent emergence of treatment resistance significantly limits the clinical efficacy of HCC immunotherapy. The molecular mechanisms underlying therapy resistance remain poorly understood.

methodsTo delineate the immune impact of nuclear factor erythroid 2-related factor 2 (Nrf2) inhibition, we integrated allograft tumor models with bulk and single-cell RNA sequencing analyses. Biochemical assays were performed to investigate the mechanisms underlying Nrf2 inhibition in immune resistance. The combined activity of Nrf2 inhibition with anti-programmed death-1 (PD-1) antibody and CAR-T cell therapy was also explored in vivo.

resultsWe show that brusatol (BRU), a specific inhibitor of Nrf2, an emerging regulator of the tumor immune microenvironment, potentiates antitumor immunity in HCC mouse models. Mechanistically, inhibition of Nrf2 downregulates surface programmed death ligand-1 (PD-L1) expression via transcriptional repression in tumor cells, while upregulating major histocompatibility complex (MHC)-I expression via nuclear factor kappa-light-chain-enhancer of activated B cells activation. Inhibition of Nrf2 in tumor cells enhances the activation of immune-related signaling pathways and promotes CD8

conclusionsOur findings offer a novel strategy to enhance HCC immunotherapy by blocking Nrf2, which has the potential to address the low response rates observed with current HCC immunotherapies.

Indexed as

Carcinoma, HepatocellularImmunotherapyLiver NeoplasmsNF-E2-Related Factor 2QuassinsAnimalsCell Line, TumorHumansImmune Checkpoint InhibitorsMicebrusatolImmune Checkpoint InhibitorsNFE2L2 protein, humanNF-E2-Related Factor 2QuassinsHepatocellular CarcinomaImmunotherapy

Identifiers

PMID41876134
PMCPMC13034291

What OpenQuestion holds

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LicenceCC BY-NC
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Registered trials

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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.