ArticlePLoS pathogens2019
Increased Programmed Death-Ligand 1 is an Early Epithelial Cell Response to Helicobacter pylori Infection.
Article in PLoS pathogens, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 115 papers, 1 of them a synthesis that pooled it.
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Who cites it
115 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Global research trends in signaling pathways of spasmolytic polypeptide-expressing metaplasia pathogenesis: a bibliometric analysis.Frontiers in oncology · 2025Pooled it
- Beyond PD-L1/PD-1: expression of PVR/TIGIT and TNFRSF14/BTLA axes in response to Helicobacter pylori and in gastric cancer lesions.ImmunoHorizons · 2026Article
- High-throughput histopathology for complex in vitro models.Cell reports methods · 2026Article
- Targeting the gut microbiota-metabolite-immune axis in cancer immunotherapy: mechanistic interplay, therapeutic strategies, and translational applications-a narrative review.Translational cancer research · 2026Review
- Walking the tightrope: Balancing immune checkpoints and their inhibitors in host defence against bacterial infections.Journal of applied biomedicine · 2026Review
- Single-cell transcriptomic comparison of the developing human fetal stomach and pluripotent stem cell-derived gastric organoids.Development (Cambridge, England) · 2026Article
- Therapeutic regulation of gut microbiota in gastric cancer: mechanisms, strategies, and clinical prospects.Frontiers in microbiology · 2026Review
- Organoid models: applications and research advances in gastric cancer.Frontiers in oncology · 2026Review
- Tumor organoid-immune cell co-culture systems for precision oncology.Frontiers in cell and developmental biology · 2026Review
- Metabolism-Driven Modulation by the Human Microbiota: Implications for Cancer Therapy and Emerging Strategies.Advances in experimental medicine and biology · 2026Review
- Myeloid-derived suppressor cells modulation in the context of tumor microenvironment for gastric cancer.Clinical & translational oncology : official publication of the Federation of Spanish Oncology Societies and of the National Cancer Institute of Mexico · 2025Review
- Intratumoral microbiota remodeling of the tumor microenvironment impact solid tumor immunotherapy.Cell death & disease · 2025Review
- Exploring compositional and predicted functional alterations of gut microbiota in H. pylori infection.Scientific reports · 2025Article
- Gut microbiome and gastric cancer: microbial interactions and therapeutic potential.Gut pathogens · 2025Review
- Advancements in understanding tumor-resident bacteria and their application in cancer therapy.Military Medical Research · 2025Review
- Organoid models in oncology: advancing precision cancer therapy and vaccine development.Cancer biology & medicine · 2025Review
- Article
- Modeling cancer-microbiome interactions in vitro: A guide to co-culture platforms.International journal of cancer · 2025Review
- Comparative models of uveitis.Eye (London, England) · 2025Review
- Helicobacter pylori is associated with less tumor-infiltrating lymphocytes and a poor prognosis in gastric cancer.BMC gastroenterology · 2025Article
55 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 1 country.
Funding
Abstract
Helicobacter pylori (H. pylori) is the major risk factor for the development of gastric cancer. Our laboratory has reported that the Sonic Hedgehog (Shh) signaling pathway is an early response to infection that is fundamental to the initiation of H. pylori-induced gastritis. H. pylori also induces programmed death ligand 1 (PD-L1) expression on gastric epithelial cells, yet the mechanism is unknown. We hypothesize that H. pylori-induced PD-L1 expression within the gastric epithelium is mediated by the Shh signaling pathway during infection. To identify the role of Shh signaling as a mediator of H. pylori-induced PD-L1 expression, human gastric organoids generated from either induced pluripotent stem cells (HGOs) or tissue (huFGOs) were microinjected with bacteria and treated with Hedgehog/Gli inhibitor GANT61. Gastric epithelial monolayers generated from the huFGOs were also infected with H. pylori and treated with GANT61 to study the role of Hedgehog signaling as a mediator of induced PD-1 expression. A patient-derived organoid/autologous immune cell co-culture system infected with H. pylori and treated with PD-1 inhibitor (PD-1Inh) was developed to study the protective mechanism of PD-L1 in response to bacterial infection. H. pylori significantly increased PD-L1 expression in organoid cultures 48 hours post-infection when compared to uninfected controls. The mechanism was cytotoxic associated gene A (CagA) dependent. This response was blocked by pretreatment with GANT61. Anti-PD-L1 treatment of H. pylori infected huFGOs, co-cultured with autologous patient cytotoxic T lymphocytes and dendritic cells, induced organoid death. H. pylori-induced PD-L1 expression is mediated by the Shh signaling pathway within the gastric epithelium. Cells infected with H. pylori that express PD-L1 may be protected from the immune response, creating premalignant lesions progressing to gastric cancer.
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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.