Impact of Tenascin-C on Radiotherapy in a Novel Syngeneic Oral Squamous Cell Carcinoma Model With Spontaneous Dissemination to the Lymph Nodes

• DOI: 10.3389/fimmu.2021.636108
• Publication Date: 2021-07-05T08:26:46Z
• Authors: Caroline Spenlé; Thomas Loustau; Hélène Burckel; Gilles Riegel; Chérine Abou Faycal; Chengbei Li; Alev Yilmaz; Luciana Petti; Fanny Steinbach; Constance Ahowesso; Camille Jost; Nicodème Paul; Raphael Carapito; Georges Noël; Fabienne Anjuère; Nathalie Salomé; Gertraud Orend
• Keywords: Tenascin C

Radiotherapy, the most frequent treatment of oral squamous cell carcinomas (OSCC) besides surgery is employed to kill tumor cells but, radiotherapy may also promote relapse where immune-suppressive microenvironment (TME) could be instrumental. We established a novel syngeneic grafting model from carcinogen-induced tongue tumor, OSCC13, address impact on OSCC. This revealed similarities with human OSCC, recapitulating mutations found in smoking associated tumors, abundant infiltrating leukocytes (TIL) and, spontaneous dissemination local lymph nodes. Cultured OSCC13 and OSCC13-derived tumors were sensitive irradiation. At chosen dose 2 Gy mimicking OSCC patients not all killed allowing investigate effects TME. By investigating expression extracellular matrix molecule tenascin-C (TNC), an indicator immune suppressive TME, we observed high TNC TIL infiltration irradiated tumors. In knockout host TME appeared less tendency towards more regression than WT conditions. Altogether, our model, sharing important features disease relevant for future anti-cancer targeting by other therapeutic approaches.