ArticleCell research2017
Chemotherapy-induced intestinal inflammatory responses are mediated by exosome secretion of double-strand DNA via AIM2 inflammasome activation.
Article in Cell research, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 116 papers, 2 of them syntheses that pooled it.
What it found
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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
116 citing papers in PubMed, 2 syntheses or guidelines pooled it, 184 citations in OpenAlex.
- The Pro-tumor and Anti-tumor Effects of NLRP3 Inflammasome as a New Therapeutic Option for Colon Cancer: a Meta-analysis of Pre-clinical Studies.Journal of gastrointestinal cancer · 2023Pooled it
- Efficacy and Safety of Thalidomide As a Pre-Medication of Chemotherapy-Induced Nausea and Vomiting (CINV) Following Highly Emetogenic Chemotherapy (HEC): A Systematic Review and Meta-Analysis.Frontiers in oncology · 2021Pooled it
- The impact of animal models on translating male infertility research from bench to bedside: a narrative review.Reproductive biology and endocrinology : RB&E · 2026Review
- The Multifaceted Role of Extracellular Vesicles in Triple Negative Breast Cancer.International journal of molecular sciences · 2026Review
- Novel insights into extracellular vesicles: An update on biomolecules, immunomodulation and clinical strategies in skin melanoma.Clinical and translational medicine · 2026Review
- A Comprehensive Review of AIM2 in Cancer: Functional Roles, Molecular Pathways, and Clinical Relevance.Journal of immunology research · 2026Review
- 80 years of extracellular vesicles: from discovery to clinical translation.Extracellular vesicles and circulating nucleic acids · 2026Review
- Circulating extracellular vesicle DNA (EV-DNA) and cell-free DNA in ovarian cancer: pathological relevance and diagnostic applications.Extracellular vesicles and circulating nucleic acids · 2026Review
- Delaying cardiac aging: potential mechanisms centered on PANoptosis and targeted intervention strategies.Frontiers in cardiovascular medicine · 2026Review
- The Role of Inflammasomes in Chronic Oral Inflammatory Disease and Oral Cancer: A Narrative Review.Dentistry journal · 2025Review
- The Immunogenic Role of Self-DNA in T Cell Immunity.Clinical reviews in allergy & immunology · 2025Review
- A Tacrolimus Population Pharmacokinetic Model for Adult Allogeneic Hematopoietic Cell Transplant Recipients Provides Clinical Opportunities for Precision Dosing.Clinical pharmacokinetics · 2025Article
- Microalgae-carrying nanomedicine for bioadhesive drug delivery for treating chemotherapy-induced intestinal injury.Asian journal of pharmaceutical sciences · 2025Article
- Role of the AIM2 Inflammasome in Cancer: Potential Therapeutic Strategies.Biomedicines · 2025Review
- Absent in melanoma 2: a potent suppressor of retinal pigment epithelial-mesenchymal transition and experimental proliferative vitreoretinopathy.Cell death & disease · 2025Article
- Conventional Chemotherapy and Inflammation: What Is the Role of the Inflammasome in the Tumor Microenvironment?Biomedicines · 2025Review
- Unique structural configuration of EV-DNA primes Kupffer cell-mediated antitumor immunity to prevent metastatic progression.Nature cancer · 2024Article
- Doxorubicin-Induced Cardiotoxicity Through SIRT1 Loss Potentiates Overproduction of Exosomes in Cardiomyocytes.International journal of molecular sciences · 2024Article
- Analyzing Extracellular Vesicle-associated DNA Using Transmission Electron Microscopy at the Single EV-level.Current protocols · 2024Article
- The detection, biological function, and liquid biopsy application of extracellular vesicle-associated DNA.Biomarker research · 2024Review
56 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 6 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chemotherapies are known often to induce severe gastrointestinal tract toxicity but the underlying mechanism remains unclear. This study considers the widely applied cytotoxic agent irinotecan (CPT-11) as a representative agent and demonstrates that treatment induces massive release of double-strand DNA from the intestine that accounts for the dose-limiting intestinal toxicity of the compound. Specifically, "self-DNA" released through exosome secretion enters the cytosol of innate immune cells and activates the AIM2 (absent in melanoma 2) inflammasome. This leads to mature IL-1β and IL-18 secretion and induces intestinal mucositis and late-onset diarrhoea. Interestingly, abrogation of AIM2 signalling, either in AIM2-deficient mice or by a pharmacological inhibitor such as thalidomide, significantly reduces the incidence of drug-induced diarrhoea without affecting the anticancer efficacy of CPT-11. These findings provide mechanistic insights into how chemotherapy triggers innate immune responses causing intestinal toxicity, and reveal new chemotherapy regimens that maintain anti-tumour effects but circumvent the associated adverse inflammatory response.
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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.