ArticleBritish journal of cancer2019
Direct therapeutic targeting of immune checkpoint PD-1 in pancreatic cancer.
Article in British journal of cancer, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 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
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 55 citations in OpenAlex.
- Organoids in translation: a bench-to-bedside framework for pancreatic cancer precision medicine.Journal of translational medicine · 2026Pooled it
- Gemcitabine and nab-paclitaxel with or without the VDR agonist paricalcitol for metastatic pancreatic cancer: a randomized, multiarm, run-in phase trial.Nature cancer · 2026Trial
- Immune Markers and Risk of Pancreatic Cancer in the European EPIC Cohort.International journal of cancer · 2026Article
- Targeted Cepharanthine-Mediated Dual-Pathway Inhibition Sensitizes Pancreatic Cancer to Gemcitabine.Life (Basel, Switzerland) · 2026Article
- IOA-244, a novel p110δ PI3K inhibitor, blocks breast tumour progression on either mono- or combined-therapy.Cell death discovery · 2026Article
- STYK1 as a targetable vulnerability enhances the efficacy of anti-PD-L1 therapy in pancreatic cancer.Journal of gastroenterology · 2025Article
- Therapeutic applications of a novel humanized monoclonal antibody targeting chemokine receptor CCR9 in pancreatic cancer.Molecular oncology · 2025Article
- The application of organoids in treatment decision-making for digestive system cancers: progress and challenges.Molecular cancer · 2025Review
- Interferon-α and thymosin-α1 plus tislelizumab enhance CD8iScience · 2025Article
- TIM-3 teams up with PD-1 in cancer immunotherapy: mechanisms and perspectives.Molecular biomedicine · 2025Review
- Patient-derived organotypic tissue cultures as a platform to evaluate metabolic reprogramming in breast cancer patients.The Journal of biological chemistry · 2025Article
- Application and challenges of tumor organoid technology in precision immunotherapy.Frontiers in immunology · 2025Review
- Development of selective ssDNA micro-probe for PD1 detection as a novel strategy for cancer imaging.Scientific reports · 2024Article
- Review
- Unveiling the functional roles of patient-derived tumour organoids in assessing the tumour microenvironment and immunotherapy.Clinical and translational medicine · 2024Review
- Type I interferon signaling induces melanoma cell-intrinsic PD-1 and its inhibition antagonizes immune checkpoint blockade.Nature communications · 2024Article
- Tumor cell-intrinsic PD-1 promotes Merkel cell carcinoma growth by activating downstream mTOR-mitochondrial ROS signaling.Science advances · 2024Article
- A combined opposite targeting of p110δ PI3K and RhoA abrogates skin cancer.Communications biology · 2024Article
- Responsive Microneedles as a New Platform for Precision Immunotherapy.Pharmaceutics · 2023Review
- Exploring the potential of exosomes in diagnosis and drug delivery for pancreatic ductal adenocarcinoma.International journal of cancer · 2023Review
Corrections and comments
- Erratum issued
Authors and funding
13 authors at 6 institutions in 1 country.
Funding
Abstract
backgroundPancreatic cancer (PC) hijacks innate cellular processes to promote cancer growth. We hypothesized that PC exploits PD-1/PD-L1 not only to avoid immune responses, but to directly enhance growth. We also hypothesized that immune checkpoint inhibitors (ICIs) have direct cytotoxicity in PC. We sought to elucidate therapeutic targeting of PD-1/PD-L1.
methodsPD-1 was assessed in PC cells, patient-derived organoids (PDOs), and clinical tissues. Then, PC cells were exposed to PD-L1 to evaluate proliferation. To test PD-1/PD-L1 signaling, cells were exposed to PD-L1 and MAPK was examined. Radio-immunoconjugates with anti-PD-1 drugs were developed to test uptake in patient-derived tumor xenografts (PDTXs). Next, PD-1 function was assessed by xenografting PD-1-knockdown cells. Finally, PC models were exposed to ICIs.
resultsPD-1 expression was demonstrated in PCs. PD-L1 exposure increased proliferation and activated MAPK. Imaging PDTXs revealed uptake of radio-immunoconjugates. PD-1 knockdown in vivo revealed 67% smaller volumes than controls. Finally, ICI treatment of both PDOs/PDTXs demonstrated cytotoxicity and anti-MEK1/2 combined with anti-PD-1 drugs produced highest cytotoxicity in PDOs/PDTXs.
conclusionsOur data reveal PCs innately express PD-1 and activate druggable oncogenic pathways supporting PDAC growth. Strategies directly targeting PC with novel ICI regimens may work with adaptive immune responses for optimal cytotoxicity.
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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.