Injury and inflammation promote cancer progression at the anorectal junction
Year: 2025
Type: article
Abstract: In anorectal cancer, epithelial tumors frequently develop in transition zones (TZs) between the anal and the rectal epithelia, a region subjected to inflammation and wounds. However, whether inflammation and wounds contribute to tumor development in the anorectal region remain totally unknown. Using mice with KRAS G12D mutation selectively at the TZ cells, we found that recurrent wound and its associated sustained inflammation are essential to promote tumor development. We characterized at the single-cell level the malignant events that occurred at the TZ all along tumor development from early neoplastic, hyperplastic, to malignant transition. We showed that this tumoral development was under the influence of interleukin (IL)-17, a cytokine highly secreted by a γδ T lymphocyte subset, allowing the recruitment of neutrophils at the TZ, which was crucial for tumor progression. Hence, this study reveals the importance of wound and its associated IL-17/neutrophil inflammatory axis in cancer progression.
Source: Cell Reports
Authors: Chloé Petitpas, Louciné Mitoyan, Valentin Thevin, Marjorie Martin, Hector Hernandez-Vargas, Véronique Chevrier, Alexane Ollivier, Muge Kaya, Flora Poizat, Marie Heinisch, Magda Rodrigues, Laetitia Gameiro-Ferreira, Jean-Philippe Ratone, Fabrice Caillol, Yanis Dahel, Solène Hoibian, Marc Giovannini, Cécile de Chaisemartin, Emmanuelle Charafe-Jauffret, Christophe Ginestier, Julien C. Marie, Géraldine Guasch
Language: English
Subfield: Surgery
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $5,620
OpenAlex ID: W4416257170