ArticleGut2023
Targeting PPAR-gamma counteracts tumour adaptation to immune-checkpoint blockade in hepatocellular carcinoma.
Article in Gut, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03419481 (A Clinical Trial of Pembrolizumab in Patients With Hepatitis B Virus-related Hepatocellular Carcinoma, With Parallel Study on Baseline and Serial Change in the Immune Environment), which is not on this map. Cited by 70 papers.
What it found
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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.
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.
A Clinical Trial of Pembrolizumab in Patients With Hepatitis B Virus-related Hepatocellular Carcinoma, With Parallel Study on Baseline and Serial Change in the Immune Environment
Who cites it
70 citing papers in PubMed, 93 citations in OpenAlex.
- 8-Chloroadenosine suppresses hepatocellular carcinoma progression via ADAR1/PPARγ axis-mediated lipid metabolism.Genes & diseases · 2026Article
- Spatial ecotype in tumor immune exclusion: from spatial architecture to therapeutic strategies.Molecular cancer · 2026Review
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- Integrated bioinformatics analysis reveals fatty acid metabolism subtypes and immune landscape in recurrent implantation failure.Scientific reports · 2026Article
- Integrated Spatial Metabolomics and Transcriptomics Decipher the Effect of Chronic Stress on the Progression of Liver Cancer.Applied biochemistry and biotechnology · 2026Article
- Pro-EGCG suppresses endometriosis progression via regulating monocytic myeloid-derived suppressor cells.Chinese medicine · 2026Article
- Prognostic analysis and beneficiary population exploration of subsequent treatment regimens after third-generation EGFR-TKIs failure in EGFR-mutated advanced non-small cell lung cancer: a retrospective cohort study.Translational lung cancer research · 2026Article
- Harnessing the microbiome for cancer therapy.Nature reviews. Microbiology · 2026Review
- Pioglitazone Attenuates Sepsis-Associated Acute Kidney Injury by Modulating TLR-4/NF-κB Signaling and Improving Survival and Renal Function.Journal of clinical medicine · 2026Article
- Cannabidiol-Ion Channel Interactions Represent a Promising Preventive and Therapeutic Strategy in Hepatocellular Carcinoma.Pathophysiology : the official journal of the International Society for Pathophysiology · 2026Review
- Targeting the E2F6-TOP2A-DKK1 axis: a novel therapeutic strategy for EMT-driven hepatocellular carcinoma progression.Frontiers in immunology · 2026Article
- Tissue and blood-based predictive biomarkers in hepatocellular carcinoma immunotherapy: synthesis of 2023-2026 evidence and a proposed clinical integration framework.Frontiers in oncology · 2026Review
- Macrophage-linked lipid metabolic signatures for HCC prognosis identified through integrated bulk and single-cell transcriptomics.Frontiers in immunology · 2026Article
- Drug resistance mechanisms of immunotherapy and translational strategies for reversing resistance for hepatocellular carcinoma: from bench to bedside.Frontiers in immunology · 2026Review
- Mechanisms of Immune Checkpoint Inhibitor Resistance in Hepatocellular Carcinoma and Strategies for Reversal.Cancers · 2025Review
- Targeting OxLDL-mediated CD36 + CAF reprogramming potentiates PD-1 immunotherapy in osteosarcoma.Molecular cancer · 2025Article
- The role of PD‑1/PD‑L1 axis in liver diseases.Clinical and experimental medicine · 2025Review
- Global research trends in liver regeneration and immunomodulation: A perspective from bibliometric analysis.Human vaccines & immunotherapeutics · 2025Article
- PPARγ, a key modulator of metabolic reprogramming, stemness and chemoresistance associated with retrodifferentiation in human hepatocellular carcinomas.Cell death & disease · 2025Article
- Wild-type KRAS activation drives evasion of interferon-mediated immunity and resistance to immunotherapy in hepatocellular carcinoma.Nature communications · 2025Article
10 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
28 authors at 3 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
objectiveTherapy-induced tumour microenvironment (TME) remodelling poses a major hurdle for cancer cure. As the majority of patients with hepatocellular carcinoma (HCC) exhibits primary or acquired resistance to antiprogrammed cell death (ligand)-1 (anti-PD-[L]1) therapies, we aimed to investigate the mechanisms underlying tumour adaptation to immune-checkpoint targeting.
designTwo immunotherapy-resistant HCC models were generated by serial orthotopic implantation of HCC cells through anti-PD-L1-treated syngeneic, immunocompetent mice and interrogated by single-cell RNA sequencing (scRNA-seq), genomic and immune profiling. Key signalling pathway was investigated by lentiviral-mediated knockdown and pharmacological inhibition, and further verified by scRNA-seq analysis of HCC tumour biopsies from a phase II trial of pembrolizumab (NCT03419481).
resultsAnti-PD-L1-resistant tumours grew >10-fold larger than parental tumours in immunocompetent but not immunocompromised mice without overt genetic changes, which were accompanied by intratumoral accumulation of myeloid-derived suppressor cells (MDSC), cytotoxic to exhausted CD8
conclusionWe uncover an adaptive transcriptional programme by which tumour cells evade immune-checkpoint targeting via PPARγ/VEGF-A-mediated TME immunosuppression, thus providing a strategy for counteracting immunotherapeutic resistance in HCC.
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Registered trials
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.