ArticleCancer immunology, immunotherapy : CII2021
PD-1/PD-L1 checkpoint inhibitors in combination with olaparib display antitumor activity in ovarian cancer patient-derived three-dimensional spheroid cultures.
Article in Cancer immunology, immunotherapy : CII, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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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
19 citing papers in PubMed, 28 citations in OpenAlex.
- Niraparib plus nivolumab or niraparib plus ipilimumab in patients with platinum-sensitive advanced pancreatic cancer: a randomised, phase 1b/2 trial.The Lancet. Oncology · 2022Trial
- Antitumor activity and structure-activity relationship of poly (ADP-ribose) polymerase (PARP)-based dual inhibitors.Journal of enzyme inhibition and medicinal chemistry · 2026Review
- The Role of Immune Checkpoint Inhibitors in Cancer Therapy: Mechanism and Therapeutic Advances.MedComm · 2025Review
- Precision Medicine in High-Grade Serous Ovarian Cancer: Targeted Therapies and the Challenge of Chemoresistance.International journal of molecular sciences · 2025Review
- Threading the Needle: Navigating Novel Immunotherapeutics in Pancreatic Ductal Adenocarcinoma.Cancers · 2025Review
- Digestive cancers: mechanisms, therapeutics and management.Signal transduction and targeted therapy · 2025Review
- Inflammation and Immune Escape in Ovarian Cancer: Pathways and Therapeutic Opportunities.Journal of inflammation research · 2025Review
- Novel frontiers in urogenital cancers: from molecular bases to preclinical models to tailor personalized treatments in ovarian and prostate cancer patients.Journal of experimental & clinical cancer research : CR · 2024Review
- Heterogeneity and treatment landscape of ovarian carcinoma.Nature reviews. Clinical oncology · 2023Review
- Exploring the promising potential of induced pluripotent stem cells in cancer research and therapy.Molecular cancer · 2023Review
- PARP14 inhibition restores PD-1 immune checkpoint inhibitor response following IFNγ-driven acquired resistance in preclinical cancer models.Nature communications · 2023Article
- Targeted therapy and immunotherapy: Diamonds in the rough in the treatment of epithelial ovarian cancer.Frontiers in pharmacology · 2023Review
- Mechanistic and pharmacodynamic studies of DuoBody-CD3x5T4 in preclinical tumor models.Life science alliance · 2022Article
- Review
- Biomarkers and 3D models predicting response to immune checkpoint blockade in head and neck cancer (Review).International journal of oncology · 2022Review
- Preclinical models for development of immune-oncology therapies.Immuno-oncology insights · 2022Article
- Current Advances in PD-1/PD-L1 Blockade in Recurrent Epithelial Ovarian Cancer.Frontiers in immunology · 2022Review
- Review
- Leveraging NKG2D Ligands in Immuno-Oncology.Frontiers in immunology · 2021Review
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune checkpoint inhibitors (ICIs) that target programmed cell death protein 1 (PD-1) and programmed death-ligand 1 (PD-L1) have shown modest activity as monotherapies for the treatment of ovarian cancer (OC). The rationale for using these therapies in combination with poly (ADP-ribose) polymerase inhibitors (PARP-Is) has been described, and their in vivo application will benefit from ex vivo platforms that aid in the prediction of patient response or resistance to therapy. This study examined the effectiveness of detecting patient-specific immune-related activity in OC using three-dimensional (3D) spheroids. Immune-related cell composition and PD-1/PD-L1 expression status were evaluated using cells dissociated from fresh OC tissue from two patients prior to and following 3D culture. The patient sample with the greatest increase in the proportion of PD-L1 + cells also possessed more activated cytotoxic T cells and mature DCs compared to the other patient sample. Upon cytokine stimulation, patient samples demonstrated increases in cytotoxic T cell activation and DC major histocompatibility complex (MHC) class-II expression. Pembrolizumab increased cytokine secretion, enhanced olaparib cytotoxicity, and reduced spheroid viability in a T cell-dependent manner. Furthermore, durvalumab and olaparib combination treatment increased cell death in a synergistic manner. This work demonstrates that immune cell activity and functional modulation can be accurately detected using our ex vivo 3D spheroid platform, and it presents evidence for their utility to demonstrate sensitivity to ICIs alone or in combination with PARP-Is in a preclinical setting.
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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.