ArticleJournal for immunotherapy of cancer2026
Targeted inhibition of Nrf2 potentiates antitumor immunity and enhances the efficacy of immunotherapy in hepatocellular carcinoma.
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.
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Who cites it
2 citing papers in PubMed.
- Nrf2 deficiency converts the ESCC microenvironment into an immunologically active state via the GPX2-ICD-DC signaling path.Journal of translational medicine · 2026Article
- Enhancing immunotherapy efficacy of hepatocellular carcinoma by inhibiting the key antioxidant factor Nrf2.Molecular therapy. Oncology · 2026Article
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Authors and funding
10 authors.
Funding
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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.
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