ArticleJournal of personalized medicine2020
Evidences of CTLA-4 and PD-1 Blocking Agents-Induced Cardiotoxicity in Cellular and Preclinical Models.
Article in Journal of personalized medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 53 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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
53 citing papers in PubMed, 1 synthesis or guideline pooled it, 64 citations in OpenAlex.
- Global trends and research hotspots of PCSK9 and cardiovascular disease: a bibliometric and visual analysis.Frontiers in cardiovascular medicine · 2024Pooled it
- A narrative review of immune checkpoint inhibitor-related cardiotoxicity in lung cancer: mechanisms, risk stratification, and clinical management.Journal of thoracic disease · 2026Review
- Heart-Type Fatty Acid-Binding Protein (H-FABP) as a Candidate Adjunctive Biomarker for Immune Checkpoint Inhibitor-Related Cardiotoxicity: Linking Early Immune-Metabolic Myocardial Injury with Translational Cardio-Oncology.International journal of molecular sciences · 2026Review
- Review
- Pathological mechanisms and treatment strategies for immune checkpoint inhibitor-associated myocarditis: insights from single-cell sequencing.Basic research in cardiology · 2026Review
- Evidence of Cardiotoxic Immune Activation by Triple Immune Checkpoint Blockade: A Translational Alert for Clinical Surveillance in Patients With Cancer.Journal of cardiovascular pharmacology · 2026Article
- Cardiovascular toxicity induced by immune checkpoint inhibitors: mechanisms linking immune dysregulation and myocardial fibrosis.American journal of clinical and experimental immunology · 2026Review
- Immune checkpoint inhibitor-related cardiotoxicity: a cellular pharmacology perspective on susceptibility and resistance.Frontiers in pharmacology · 2026Review
- A review of immune checkpoint inhibitor-associated myocarditis: Epidemiology, pathogenesis, and biomarkers.Human vaccines & immunotherapeutics · 2025Review
- MLKL-Mediated Necroptosis Predominantly Contributes to Immune-Associated Myocardial Damage.Inflammation · 2025Article
- Review
- Cardio-Renal and Systemic Effects of SGLT2i Dapagliflozin on Short-Term Anthracycline and HER-2-Blocking Agent Therapy-Induced Cardiotoxicity.Antioxidants (Basel, Switzerland) · 2025Article
- From Bench to Bedside: Translational Approaches to Cardiotoxicity in Breast Cancer, Lung Cancer, and Lymphoma Therapies.Cancers · 2025Review
- Molecular fingerprints of cardiovascular toxicities of immune checkpoint inhibitors.Basic research in cardiology · 2025Review
- Changes in tumor and cardiac metabolism upon immune checkpoint.Basic research in cardiology · 2025Review
- Targeting the NLRP3 inflammasome abrogates cardiotoxicity of immune checkpoint blockers.Journal for immunotherapy of cancer · 2025Article
- The role of immune checkpoints PD-1 and CTLA-4 in cardiovascular complications leading to heart failure.Frontiers in immunology · 2025Review
- From tumor to tolerance: A comprehensive review of immune checkpoint inhibitors and immune-related adverse events.Asia Pacific allergy · 2024Review
- Immune checkpoints in cardiac physiology and pathology: therapeutic targets for heart failure.Nature reviews. Cardiology · 2024Review
- The Association between Major Adverse Cardiovascular Events and Peripheral Artery Disease Burden.Journal of cardiovascular development and disease · 2024Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundSeveral strategies based on immune checkpoint inhibitors (ICIs) have been developed for cancer therapy, opening to advantages in cancer outcomes. However, several ICI-induced side effects have emerged in these patients, especially a rare but clinically significant cardiotoxicity with high rate of mortality. We studied the cytotoxic and pro-inflammatory properties of Ipilimumab and Nivolumab, the underlying pathways and cytokine storm involved.
methodsCo-cultures of human cardiomyocytes and lymphocytes were exposed to Ipilimumab or Nivolumab; cell viability and expression of leukotrienes, NLRP3, MyD88, and p65/NF-kB were performed. C57 mice were treated with Ipilimumab (15 mg/kg); analysis of fractional shortening, ejection fraction, radial and longitudinal strain were made before and after treatments through 2D-echocardiography. Expression of NLRP3, MyD88, p65/NF-kB, and 12 cytokines were analyzed in murine myocardium.
resultsNivolumab and Ipilimumab exert effective anticancer, but also significant cardiotoxic effects in co-cultures of lymphocytes and tumor or cardiac cells. Both ICIs increased NLRP3, MyD88, and p65/NF-kB expression compared to untreated cells, however, the most pro-inflammatory and cardiotoxic effects were seen after exposure to Ipilimumab. Mice treated with Ipilimumab showed a significant decrease in fractional shortening and radial strain with respect to untreated mice, coupled with a significant increase in myocardial expression of NLRP3, MyD88, and several interleukins.
conclusionsNivolumab and Ipilimumab exert cytotoxic effects mediated by the NLRP3/IL-1β and MyD88 pathways, leading to pro-inflammatory cytokine storm in heart tissue.
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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.