Tenascin-C orchestrates radiotherapy-induced head and neck tumor regression.

Fiche publication

Date publication

mars 2026

Journal

EMBO molecular medicine

Auteurs

Membres identifiés du Cancéropôle Est :
Pr NOEL Georges , Dr OREND Gertraud , Dr CARAPITO Christine , Dr CARAPITO Raphaël , Dr BURCKEL Hélène , Dr SALOME Nathalie

Tous les auteurs :
Loustau T, Mitrentsi I, Wang N, Spenlé C, Pavlidaki A, Tranchant T, Riegel G, Venu A, Oueidat R, Koch M, Dumas M, Wack F, Hirschler A, Carapito C, Paul N, Carapito R, Mörgelin M, Hansen U, Azzi J, Aubergeon L, Salomé N, Dhaouadi S, Grenot P, Bouhaouala-Zahar B, La Cioppa S, Oertle P, Izzi V, Plodinec M, Noel G, Burckel H, Orend G

Lien Pubmed

https://www.ncbi.nlm.nih.gov/pubmed/41917325

Résumé

Given that head and neck squamous cell carcinoma (HNSCC) patients have poor survival outcomes, a better understanding of the therapeutic benefits of ionizing irradiation (IR), the major treatment modality besides surgery, is needed. A confounding factor is the immunosuppressive tumor microenvironment determined by tenascin-C (TNC), a highly abundant extracellular matrix molecule upregulated by IR. We investigated the roles of TNC on radio-induced tumor regression in a murine oral HNSCC model expressing or lacking TNC. While tumors in a TNC-expressing host were radiosensitive, they were radioresistant in TNC genetically depleted mice. We identified fibroblast reticular cells (FRCs) as critical regulators. TNC plays a compartmentalized and dual role in regulating tumor radiosensitivity with a detrimental role in the tumor stroma opposed to an essential role in the tumor-draining lymph nodes. This is relevant as a high FRC signature and high TNC levels together correlate with shorter HNSCC patient survival. TNC-expressing FRCs may be an excellent novel target to improve radiotherapy-induced tumor eradication, as our TNC targeting MAREMO peptide reduced tumor cell numbers and plasticity upon IR.