ArticleCell death & disease2021
Gut-derived lipopolysaccharide remodels tumoral microenvironment and synergizes with PD-L1 checkpoint blockade via TLR4/MyD88/AKT/NF-κB pathway in pancreatic cancer.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
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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.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 88 citations in OpenAlex.
- Global research trends and focus on biomarkers in lung cancer immunotherapy: a comprehensive bibliometric insight and visualization analysis (2001-2025).Frontiers in immunology · 2026Pooled it
- Microbiota as a modulator of drug response: targeting microbial-drug crosstalk in cancer therapy.Gut microbes · 2026Review
- Leveraging the bacteria for enhanced cancer immunotherapy: from a perspective of synthetic biology.Cancer biology & therapy · 2026Review
- Review
- Microbiome: a driver of pancreatic inflammation and tumorigenesis.Trends in cancer · 2026Review
- Gut microbiota modulation of gastrointestinal cancers: from dysbiosis signatures to therapeutic interventions.Acta pharmacologica Sinica · 2026Review
- Can Complex 3D Models Effectively Replace 2D and Animal Models to Investigate the Microbe-Tumor-Immune Axis in Pancreatic Cancer Studies?Nutrients · 2026Review
- Single-Cell Transcriptomic Mapping of PD-L1/TLR4 Remodeling Informs Topical Immunoprevention Timing in Skin Carcinogenesis.bioRxiv : the preprint server for biology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Microwave ablation synergizes with LPS to drive abscopal tumor regression associated with ferroptosis in HCC.iScience · 2026Article
- Gut microbiota and pancreatic cancer: tumorigenesis, progression, and clinical applications.Cancer biology & medicine · 2026Review
- Pancreatic Cancer in the Holobiont and Therapeutic Targets: A Review.Journal of clinical medicine · 2026Review
- Exploring the role of metabolic disorders and gut microbiome in immune checkpoint regulation in cancer: PI3K/AKT/mTOR focus.Journal of physiology and biochemistry · 2026Review
- Mechanistic insights into pancreatic cancer progression from circadian rhythm disruption and gut microbiota dysbiosis (Review).International journal of molecular medicine · 2026Review
- The gut-liver-virus axis in hepatitis B and C: microbiota, immunometabolism, and exosome-mediated therapeutic opportunities.Naunyn-Schmiedeberg's archives of pharmacology · 2026Review
- TLR4 promotes ESCC progression by driving inflammation and metabolic reprogramming through SLC39A10-mediated zinc homeostasis.Journal of translational medicine · 2026Article
- Targeting Microbiome-Derived Exosomes to Overcome Cancer Therapy Resistance: Mechanisms, Implications, and Opportunities.Mini reviews in medicinal chemistry · 2026Review
- Microbiota and lipid mediators: from molecular crosstalk to therapeutic opportunities.Frontiers in pharmacology · 2026Review
- Microbiota-derived metabolic priming of CAR-T cell fitness: a translational framework for next-generation cell therapy.Frontiers in immunology · 2026Review
- Gastrointestinal cancer: molecular pathogenesis and targeted therapy.Molecular biomedicine · 2025Review
6 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
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Lipopolysaccharide (LPS) as an important inflammatory mediator activates the innate/adaptive immune system. The existence of LPS in pancreatic ductal adenocarcinoma (PDAC) has been reported, however, its biological function in PDAC remains unclear. Here, we demonstrated that circulating and tumoral LPS was significantly increased by intestinal leakage in the orthotopic murine PDAC model, and LPS administration promoted T cell infiltration but exhaustion paradoxically in the subcutaneous murine PDAC model. By bioinformatic analysis, Toll-like receptor 4 (TLR4), LPS receptor, was further found to enrich in immune tolerance signaling in PDAC tissues. Then, a significant positive correlation was found between TLR4 and programmed death ligand-1 (PD-L1) in clinical PDAC tissues, as well as serum LPS and tumoral PD-L1. Meanwhile, LPS stimulation in vitro and in vivo obviously upregulated tumor PD-L1 expression, and effectively promoted cancer cells resistance to T cell cytotoxicity. Mechanistically, the activation of TLR4/MyD88/AKT/NF-κB cascade was found to participate in LPS mediated PD-L1 transcription via binding to its promoter regions, which was enhanced by crosstalk between NF-κB and AKT pathways. Finally, PD-L1 blockade could significantly reverse LPS-induced immune escape, and synergized with LPS treatment. Taken together, LPS can remodel tumor microenvironment, and synergize with PD-L1 blockade to suppress tumor growth, which may be a promising comprehensive strategy for PDAC.
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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.