Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma.
| العنوان: | Eosinophils exert direct and indirect anti-tumorigenic effects in the development of esophageal squamous cell carcinoma. |
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| المؤلفون: | Jacobse J, Aziz Z, Sun L, Chaparro J, Pilat JM, Kwag A, Buendia M, Wimbiscus M, Nasu M, Saito T, Mine S, Orita H, Revetta F, Short SP, Washington MK, Hiremath G, Gibson MK, Coburn L, Koyama T, Goettel JA, Williams CS, Choksi YA |
| المصدر: | BioRxiv : the preprint server for biology [bioRxiv] 2023 Jun 05. Date of Electronic Publication: 2023 Jun 05. |
| نوع المنشور: | Preprint |
| اللغة: | English |
| بيانات الدورية: | Country of Publication: United States NLM ID: 101680187 Publication Model: Electronic Cited Medium: Internet NLM ISO Abbreviation: bioRxiv Subsets: PubMed not MEDLINE |
| مستخلص: | Background/aims: Eosinophils are present in several solid tumors and have context-dependent function. Our aim is to define the contribution of eosinophils in esophageal squamous cell carcinoma (ESCC), since their role in ESCC is unknown. Methods: Eosinophils were enumerated in tissues from two ESCC cohorts. Mice were treated with 4-nitroquinolone-1-oxide (4-NQO) for 8 weeks to induce pre-cancer or 16 weeks to induce carcinoma. Eosinophil number was modified by monoclonal antibody to IL-5 (IL5mAb), recombinant IL-5 (rIL-5), or genetically with eosinophil-deficient (ΔdblGATA) mice or mice deficient in eosinophil chemoattractant eotaxin-1 ( Ccl11 -/- ). Esophageal tissue and eosinophil specific RNA-sequencing was performed to understand eosinophil function. 3-D co-culturing of eosinophils with pre-cancer or cancer cells was done to ascertain direct effects of eosinophils. Results: Activated eosinophils are present in higher numbers in early stage versus late stage ESCC. Mice treated with 4-NQO exhibit more esophageal eosinophils in pre-cancer versus cancer. Correspondingly, epithelial cell Ccl11 expression is higher in mice with pre-cancer. Eosinophil depletion using three mouse models ( Ccl11 -/- mice, ΔdblGATA mice, IL5mAb treatment) all display exacerbated 4-NQO tumorigenesis. Conversely, treatment with rIL-5 increases esophageal eosinophilia and protects against pre-cancer and carcinoma. Tissue and eosinophil RNA-sequencing revealed eosinophils drive oxidative stress in pre-cancer. In vitro co-culturing of eosinophils with pre-cancer or cancer cells resulted in increased apoptosis in the presence of a degranulating agent, which is reversed with N-acetylcysteine, a reactive oxygen species (ROS) scavenger. ΔdblGATA mice exhibited increased CD4 T cell infiltration, IL-17, and enrichment of IL-17 pro-tumorigenic pathways. Conclusion: Eosinophils likely protect against ESCC through ROS release during degranulation and suppression of IL-17. |
| التعليقات: | Update in: Cell Mol Gastroenterol Hepatol. 2023 Aug 11;:. (PMID: 37574015) |
| تواريخ الأحداث: | Date Created: 20230619 Latest Revision: 20240201 |
| رمز التحديث: | 20240201 |
| مُعرف محوري في PubMed: | PMC10274643 |
| DOI: | 10.1101/2023.06.01.543287 |
| PMID: | 37333285 |
| قاعدة البيانات: | MEDLINE |
| DOI: | 10.1101/2023.06.01.543287 |
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