ArticlePloS one2021
A novel mouse model for checkpoint inhibitor-induced adverse events.
Article in PloS one, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.
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Who cites it
48 citing papers in PubMed, 58 citations in OpenAlex.
- Nivolumab plus ipilimumab induce hyper-progression in renal medullary carcinoma: results of a phase II trial and preclinical evidence.Nature communications · 2025Trial
- Prednisolone modulates CD8⁺ and regulatory T-cell activity to dampen response to immune checkpoint inhibitor therapy in melanoma.Oncoimmunology · 2026Article
- Engineering bispecific exosome activators of T cells to target immune checkpoint inhibitor-resistant metastatic melanoma.Nature biotechnology · 2026Article
- Macrophage-CD8medRxiv : the preprint server for health sciences · 2026Article
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- Co-Formulation of Pembrolizumab Murine Surrogate RMP1-14 with ImagentPharmaceutics · 2026Article
- C-type lectin domain family 5 member A-mediated activation of macrophages via a bispecific antibody enhances anti-HER2 therapy.Journal for immunotherapy of cancer · 2026Article
- Circulating exhausted CD8+ effector memory cells differentiate immune checkpoint inhibitor-induced liver injury from other acute immune-mediated liver injuries.Journal for immunotherapy of cancer · 2026Article
- Optimizing anti-PI3Kδ and anti-LAG-3 immunotherapy dosing regimens in a mouse model of triple-negative breast cancer improves outcome by removing treatment-related adverse events.Journal for immunotherapy of cancer · 2026Article
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Synergy between TLR3-ligand and IFN-α in the transient sensitization of "Cold" tumors to PD-1 blockade and the induction of systemic immunity.Journal for immunotherapy of cancer · 2025Article
- In Vivo Evaluation of PamJournal of peptide science : an official publication of the European Peptide Society · 2025Article
- Corticosteroid premedication on anti-tumor effect of immune checkpoint blockade in murine hepatocellular carcinoma models.Journal for immunotherapy of cancer · 2025Article
- Immune-mediated liver injury from checkpoint inhibitors: mechanisms, clinical characteristics and management.Nature reviews. Gastroenterology & hepatology · 2025Review
- A yeast-based oral therapeutic delivers immune checkpoint inhibitors to reduce intestinal tumor burden.Cell chemical biology · 2025Article
- Functional differences between rodent and human PD-1 linked to evolutionary divergence.Science immunology · 2025Article
- Optimal control of combination immunotherapy for a virtual murine cohort in a glioblastoma-immune dynamics model.Journal of theoretical biology · 2024Article
- In vivo dendritic cell reprogramming for cancer immunotherapy.Science (New York, N.Y.) · 2024Article
- Caspase-1-dependent spatiality in triple-negative breast cancer and response to immunotherapy.Nature communications · 2024Article
- Optimal control of combination immunotherapy for a virtual murine cohort in a glioblastoma-immune dynamics model.bioRxiv : the preprint server for biology · 2024Article
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Immune checkpoint inhibitors have demonstrated significant efficacy in the treatment of a variety of cancers, however their therapeutic potential is limited by abstruse immune related adverse events. Currently, no robust animal model exists of checkpoint inhibitor-induced adverse events. Establishing such a model will improve our mechanistic understanding of this process, which in turn will inform design of improved therapies. We developed a mouse model to determine inflammatory toxicities in response to dual checkpoint blockade in the presence of syngeneic tumors. Mice from susceptible genetic backgrounds received intraperitoneal injections of anti-mouse PD-1 and CTLA-4 antibodies. The mice were monitored for weight loss and histologic evidence of inflammation. Blood was collected for basic metabolic panels and titers of anti-nuclear antibodies. In parallel, mice were also treated with prednisolone, which is commonly used to treat immune related adverse events among cancer patients. Among all the genetic backgrounds, B6/lpr mice treated with anti-CTLA-4 and anti-PD-1 antibodies developed more substantial hepatitis, pancreatitis, colitis, and pneumonitis characterized by organ infiltration of immune cells. Mice that developed tissue infiltration demonstrated high serum levels of glucose and high titers of anti-nuclear antibodies. Finally, while administration of prednisolone prevented the development of the inflammatory adverse events, it also abrogated the protective anti-tumor effect of the checkout inhibitors. Genetic background and treatment modalities jointly modified the inflammatory adverse events in tumor bearing mice, suggesting a complex mechanism for checkpoint inhibitor-related inflammation. Future studies will assess additional genetic susceptibility factors and will examine possible contributions from the administration of other anti-inflammatory drugs.
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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.