Injury and inflammation promote cancer progression at the anorectal junction
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<sup>G12D</sup> 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.
Authors
- Flora Poizat (ORCID: https://orcid.org/0000-0002-1604-3422)
- Valentin Thevin (ORCID: https://orcid.org/0000-0002-0548-1160)
- Emmanuelle Charafe‐Jauffret (ORCID: https://orcid.org/0000-0002-0286-1299)
- Marie Heinisch
- Fabrice Caillol (ORCID: https://orcid.org/0000-0002-4186-0942)
- Magda Rodrigues (ORCID: https://orcid.org/0000-0002-8082-7141)
- Véronique Chevrier (ORCID: https://orcid.org/0000-0001-5692-3398)
- Julien C. Marie (ORCID: https://orcid.org/0000-0001-6713-7923)
- Christophe Ginestier (ORCID: https://orcid.org/0000-0002-7477-3837)
- Héctor Hernández‐Vargas (ORCID: https://orcid.org/0000-0001-6045-2103)
- Yanis Dahel
- Louciné Mitoyan (ORCID: https://orcid.org/0000-0002-1808-1713)
- Géraldine Guasch (ORCID: https://orcid.org/0000-0001-7362-9318)
- Alexane Ollivier (ORCID: https://orcid.org/0000-0002-2778-017X)
- Müge Mavioğlu Kaya (ORCID: https://orcid.org/0000-0003-1276-3745)
- Solène Hoibian
- Cécile de Chaisemartin (ORCID: https://orcid.org/0000-0001-6834-8378)
- Marjorie Martin
- Chloé Petitpas
- Marc Giovannini (ORCID: https://orcid.org/0000-0002-4382-729X)
- Jean‐Philippe Ratone
- Laetitia Gameiro-Ferreira
Institutions
- Université Claude Bernard Lyon 1 (FR)
- Centre National de la Recherche Scientifique (FR)
- Inserm (FR)
- Centre de Recherche en Cancérologie de Lyon (FR)
- Centre de Recherche en Cancérologie de Marseille (FR)
- Institut Paoli-Calmettes (FR)
Publication Details
- Journal
- Cell Reports
- Published
- 2025-11-01
- DOI
- https://doi.org/10.1016/j.celrep.2025.116552
- Primary Topic
- Immune cells in cancer
- Type
- article
- Field-Weighted Citation Impact
- 0.00