ArticleCancer medicine2024
Establishment of an animal model of immune-related adverse events induced by immune checkpoint inhibitors.
Article in Cancer medicine, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- The lethal symbiont: exploring the pathophysiology of cancer.Physiological reviews · 2026Review
- When Checkpoint Inhibitors Break Barriers: Mechanisms and Challenges of irAEs of the Skin, Gastrointestinal Tract, and Lung.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Review
- Walnut Green Husk Polysaccharide Improve Gut Microbiota and Alleviate Intestinal Inflammation Caused by Immune Checkpoint Inhibitors.Current issues in molecular biology · 2026Article
- IL-1β blockade prevents cardiotoxicity and improves the efficacy of immune checkpoint blockers and chemotherapy against pancreatic cancer in mice with obesity.Journal for immunotherapy of cancer · 2025Article
- Corticosteroid premedication on anti-tumor effect of immune checkpoint blockade in murine hepatocellular carcinoma models.Journal for immunotherapy of cancer · 2025Article
- Establishment of an animal model of immune-related adverse events induced by immune checkpoint inhibitors.Cancer medicine · 2024Article
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Authors and funding
11 authors.
Funding
Abstract
objectiveImmunotherapy, specifically immune checkpoint inhibitors (ICIs), has revolutionized cancer treatment. However, it can also cause immune-related adverse events (irAEs). This study aimed to develop a clinically practical animal model of irAEs using BALB/c mice.
methodsSubcutaneous tumors of mouse breast cancer 4T1 cells were generated in inbred BALB/c mice. The mice were treated with programmed death-1 (PD-1) and cytotoxic t-lymphocyte antigen 4 (CTLA-4) inhibitors once every 3 days for five consecutive administration cycles. Changes in tumor volume and body weight were recorded. Lung computed tomography (CT) scans were conducted. The liver, lungs, heart, and colon tissues of the mice were stained with hematoxylin-eosin (H&E) staining to observe inflammatory infiltration and were scored. Serum samples were collected, and enzyme-linked immunosorbent assay (ELISA) was used to detect the levels of ferritin, glutamic-pyruvic transaminase (ALT), tumor necrosis factor-α (TNF-α), interferon-gamma (IFN-γ), and interleukin-6 (IL-6). Mouse liver and lung cell suspensions were prepared, and changes in macrophages, T cells, myeloid-derived suppressor cells (MDSCs), and regulatory (Treg) cells were detected by flow cytometry.
resultsMice treated with PD-1 and CTLA-4 inhibitors showed significant reductions in tumor volume and body weight. The tissue inflammatory scores in the experimental group were significantly higher than those in the control group. Lung CT scans of mice in the experimental group showed obvious inflammatory spots. Serum levels of ferritin, IL-6, TNF-α, IFN-γ, and ALT were significantly elevated in the experimental group. Flow cytometry analysis revealed a substantial increase in CD3
conclusionsThe irAE-related animal model was successfully established in BALB/c mice using a combination of PD-1 and CTLA-4 inhibitors through multiple administrations with clinical translational value and practical. This model offers valuable insights into irAE mechanisms for further investigation.
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