ArticleJournal for immunotherapy of cancer2025
IL-1β blockade prevents cardiotoxicity and improves the efficacy of immune checkpoint blockers and chemotherapy against pancreatic cancer in mice with obesity.
Article in Journal for immunotherapy of cancer, 2025. 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.
- Research advances on tumor-associated macrophages in pancreatic cancer.Biochemistry and biophysics reports · 2026Review
- Understanding the Interplay Between Obesity and Cancer: From Mechanisms to Therapeutic Opportunities.Cancers · 2026Review
- Obesity-induced metabolic reprogramming of the tumor immune microenvironment: mechanisms, spatial niches, and immunotherapy response.Frontiers in immunology · 2026Review
- Comprehensive safety analysis of the clinical spectrum of adverse events associated with immune checkpoint inhibitors based on FAERS.Frontiers in immunology · 2026Article
- Overcoming impaired antigen presentation in tumor-draining lymph nodes facilitates immunotherapy.Journal for immunotherapy of cancer · 2025Article
- Cytokine profiling of patients with immune checkpoint inhibitor-associated myocarditis: a pilot study.Molecular biology reports · 2025Article
Corrections and comments
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Authors and funding
11 authors.
Funding
Abstract
backgroundImmune checkpoint blockers (ICBs) have revolutionized cancer therapy, yet they remain largely ineffective in treating pancreatic ductal adenocarcinoma (PDAC). Moreover, ICBs can cause severe immune-related adverse events (irAEs), including fatal cardiac toxicity. Finally, obesity is a risk factor in PDAC that may differentially modulate ICB efficacy in a malignancy-dependent manner.
methodsWe investigated the mechanisms underlying irAEs induced by dual ICB therapy and sought to identify strategies to mitigate them while improving ICB efficacy in the obese setting. To this end, we used a clinically relevant mouse model that integrated key features of human PDAC: (1) high-fat diet-induced obesity, (2) an orthotopic PDAC, and (3) a therapeutic regimen combining chemotherapy (FOLFIRINOX) with ICBs (α-programmed cell death protein-1 + α-cytotoxic T-lymphocyte associated protein-4 antibodies).
resultsObese mice developed cardiac irAEs and had elevated serum interleukin (IL)-1β levels after chemoimmunotherapy. IL-1β blockade not only prevented myocarditis and reduced cardiac fibrosis but also enhanced the antitumor efficacy of the combination of chemotherapy plus dual ICB therapy and significantly improved the overall survival of PDAC-bearing obese mice.
conclusionsOur findings provide the rationale and compelling data to test a Food and Drug Administration-approved anti-IL-1β antibody in combination with chemotherapy and dual ICB therapy in patients with pancreatic cancer with obesity.
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