ArticleFrontiers in immunology2023
Antibody-dependent cellular cytotoxicity-inducing antibodies enhance the natural killer cell anti-cancer response against patient-derived pancreatic cancer organoids.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers, 1 of them a synthesis that pooled it.
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14 citing papers in PubMed, 1 synthesis or guideline pooled it, 18 citations in OpenAlex.
- MASCC/ISOO Clinical Practice Statement: management of oral complications of immunotherapy.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Guideline
- Cancer cell-selective ectopic expression of CD20 as an antigen enables rituximab repurposing for solid tumour immunotherapy.Clinical and translational medicine · 2026Article
- Organoids in cancer therapy: translational applications and clinical promise.Molecular cancer · 2026Review
- Methods and applications of patient-derived organoid models for immune microenvironment and immunotherapy research in multiple cancer types.Experimental hematology & oncology · 2026Review
- High levels of circulating miR-19a-3p in patients with metastatic HER2 + breast cancer are associated with a favorable prognosis and anti-tumor immune responses.Breast cancer research : BCR · 2026Article
- Cytokine preactivation and ADCC: a potent strategy for enhancing human NK cell effector functions against 3D tumor models.Frontiers in immunology · 2026Article
- Current Advances in Preclinical Patient-Derived Cultivation Models for Individualized Drug Response Prediction in Pancreatic Cancer.Oncology research · 2026Review
- Applications and challenges of patient-derived organoids in hepatobiliary and pancreatic cancers.World journal of gastroenterology · 2025Review
- Current Organoid Culture Systems in Pancreatic Cancer.Current topics in medicinal chemistry · 2025Review
- A New Perspective on Precision Medicine: The Power of Digital Organoids.Biomaterials research · 2025Review
- The use of organoids in creating immune microenvironments and treating gynecological tumors.Journal of translational medicine · 2024Review
- The Role of Chemokines in Orchestrating the Immune Response to Pancreatic Ductal Adenocarcinoma.Cancers · 2024Review
- Graphene Oxide Nanoparticles and Organoids: A Prospective Advanced Model for Pancreatic Cancer Research.International journal of molecular sciences · 2024Review
- The Prospect of Harnessing the Microbiome to Improve Immunotherapeutic Response in Pancreatic Cancer.Cancers · 2023Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Introduction: Pancreatic cancer is associated with poor prognosis, and limited treatment options are available for the majority of patients. Natural killer (NK) cells in combination with antibodies inducing antibody-dependent cell-mediated cytotoxicity (ADCC) could be a highly effective new therapeutic option in pancreatic cancer. Accurate predictive preclinical models are needed to develop successful NK cell immunotherapy. Tumor organoids, in vitro 3D organ-like structures that retain important pathophysiological characteristics of the in vivo tumor, may provide such a model. In the current study, we assessed the cytotoxic potential of adoptive NK cells against human pancreatic cancer organoids. We hypothesized that NK cell anti-tumor responses could be enhanced by including ADCC-triggering antibodies. Methods: We performed cytotoxicity assays with healthy donor-derived IL-2-activated NK cells and pancreatic cancer organoids from four patients. A 3D cytotoxicity assay using live-cell-imaging was developed and enabled real-time assessment of the response. Results: We show that NK cells migrate to and target pancreatic cancer organoids, resulting in an increased organoid death, compared to the no NK cell controls (reaching an average fold change from baseline of 2.1±0.8 vs 1.4±0.6). After 24-hours of co-culture, organoid 2D growth increased. Organoids from 2 out of 4 patients were sensitive to NK cells, while organoids from the other two patients were relatively resistant, indicating patient-specific heterogeneity among organoid cultures. The ADCC-inducing antibodies avelumab (anti-PD-L1) and trastuzumab (anti-HER2) increased NK cell-induced organoid cell death (reaching an average fold change from baseline of 3.5±1.0 and 4.5±1.8, respectively). Moreover, combination therapy with avelumab or trastuzumab resulted in complete disintegration of organoids. Finally, inclusion of ADCC-inducing antibodies was able to overcome resistance in NK-organoid combinations with low or no kill. Discussion: These results support the use of organoids as a relevant and personalized model to study the anti-tumor response of NK cells
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