ArticleJournal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer2018
PD-1 Modulates Radiation-Induced Cardiac Toxicity through Cytotoxic T Lymphocytes.
Article in Journal of thoracic oncology : official publication of the International Association for the Study of Lung Cancer, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 71 papers, 1 of them a synthesis that pooled it.
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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.
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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
71 citing papers in PubMed, 1 synthesis or guideline pooled it, 109 citations in OpenAlex.
- Effects of confounding and effect-modifying lifestyle, environmental and medical factors on risk of radiation-associated cardiovascular disease.BMC public health · 2024Pooled it
- MicroRNAs and Alarmins in Cardio-Oncology: Biomarkers and Therapeutic Implications in Skin and Breast Cancer.International journal of molecular sciences · 2026Review
- Chest Pain With Immune Checkpoint Inhibitor Therapy: Harnessing the Power of Multimodality Imaging.JACC. Case reports · 2026Article
- PD-1/PD-L1 inhibitor induces systemic inflammation and alters cardiac lipid metabolism in C57BL/6 J mice.Human cell · 2026Article
- Radiotherapy and Cardiovascular Disease Survival Risk in Non-Small Cell Lung Cancer: A Population-Based Study From the Surveillance, Epidemiology, and End Results Database.Cancer medicine · 2026Article
- Decoding the Cardiac Immune Microenvironment and Fibroblast Crosstalk in Radiotherapy Combined with Immunotherapy-Induced Cardiac Fibrosis Based on Single-Cell Transcriptomic Analysis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- The Impact of Adjuvant Radiotherapy Combined With Targeted or Immunotherapy on the Heart in Breast Cancer.Thoracic cancer · 2026Review
- HMGB1 blockade attenuates cardiac injury induced by radiotherapy combined with PD-1 inhibitor while maintaining the anti-tumor efficacy.Apoptosis : an international journal on programmed cell death · 2026Article
- Cardiac radiosensitivity in the era of thoracic chemoradiotherapy and immunotherapy: a scoping review.The Lancet. Oncology · 2026Article
- Cardiovascular toxicity induced by immune checkpoint inhibitors: mechanisms linking immune dysregulation and myocardial fibrosis.American journal of clinical and experimental immunology · 2026Review
- Immunotherapy-associated Cardiotoxicity: a Comprehensive Review of Checkpoint inhibitors, monoclonal, cellular, and cytokine-based Treatments.Current treatment options in oncology · 2025Review
- A review of immune checkpoint inhibitor-associated myocarditis: Epidemiology, pathogenesis, and biomarkers.Human vaccines & immunotherapeutics · 2025Review
- Unmasking the Rare but Lethal Cardiac Complications of Immune Checkpoint Inhibitor Therapy: A Review of Mechanisms, Risk Factors, and Management Strategies.Current treatment options in oncology · 2025Review
- Preclinical mouse models of immune checkpoint inhibitor-associated myocarditis.Nature cardiovascular research · 2025Review
- Preclinical models of cardiotoxicity from immune checkpoint inhibitor therapy.Basic research in cardiology · 2025Review
- Cardiac toxicity and intervention strategies during thoracic cancer radiotherapy.Frontiers in oncology · 2025Review
- Factors associated with immune‑related severe adverse events (Review).Molecular and clinical oncology · 2025Review
- The Good (Tumor Killing) and the Bad (Cardiovascular Complications) of Immunologic Checkpoint Inhibitors.Current cardiology reports · 2024Review
- Article
- Cellular Alterations in Immune Checkpoint Inhibitor Therapy-Related Cardiac Dysfunction.Current heart failure reports · 2024Review
11 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 4 institutions in 2 countries.
Funding
Abstract
introductionCombined immune checkpoint blockade has led to rare autoimmune complications, such as fatal myocarditis. Recent approvals of several anti-programmed death 1 (anti-PD-1) drugs for lung cancer treatment prompted ongoing clinical trials that directly combine PD-1 inhibitors with thoracic radiotherapy for locally advanced lung cancer. Overlapping toxicities from either modality have the potential to increase the risk for radiation-induced cardiotoxicity (RICT), which is well documented among patients with Hodgkin's disease and breast cancer.
methodsTo investigate cardiotoxicity without the compounding pulmonary toxicity from thoracic radiotherapy, we developed a technique to deliver cardiac irradiation (CIR) in a mouse model concurrently with PD-1 blockade to determine the presence of cardiac toxicity by using physiological testing and mortality as end points along with histological analysis.
resultsWe observed an acute mortality of 30% within 2 weeks after CIR plus anti-PD-1 antibody compared with 0% from CIR plus immunoglobulin G (p = 0.023). Physiological testing demonstrated a reduced left ventricular ejection fraction (p < 0.01) by echocardiogram. Tissue analyses revealed increased immune cell infiltrates within cardiac tissue. Depletion of CD8-positive lymphocytes with anti-CD8 antibody reversed the acute mortality, suggesting that the toxicity is CD8-positive cell-mediated. To validate these findings using a clinically relevant fractionated radiotherapy regimen, we repeated the study by delivering five daily fractions of 6 Gy. Similar mortality, cardiac dysfunction, and histological changes were observed in mice receiving fractionated radiotherapy with concurrent anti-PD-1 therapy.
conclusionsThis study provides strong preclinical evidence that radiation-induced cardiotoxicity is modulated by the PD-1 axis and that PD-1 blockade should be administered with careful radiotherapy planning with an effort of reducing cardiac dose.
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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.