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

Abstract

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

KIF14 acts as a prognostic biomarker correlates with LCP2/ ITGAMN/ immune cell infiltration in oral squamous cell carcinoma

“…The tumor immune microenvironment has been highly researched(26). Lots of evidences showed OSCC is an immune-suppressive disease (27). Immunotherapy is a novel approach for restoring anti-tumor immune responses and overcoming tumor cell immune escape mechanisms(28).…”

Identification of Immune-Related Genes Associated With Bladder Cancer Based on Immunological Characteristics and Their Correlation With the Prognosis

“…PDGFRA (platelet derived growth factor receptor alpha) mutations cause a variety of heterogeneous gastrointestinal mesenchymal tumors (Ricci et al, 2015), and TKIs inhibiting the most common driving mutations in KIT or PDGFRA might have brought about radical changes in treating gastrointestinal stromal tumors in the past 20 years (Zalcberg, 2021). TNC (enascin-C) is a large extracellular matrix glycoprotein that promotes cell adhesion and tissue remodeling, and is involved in the transduction of cellular signaling pathways (Spenlé et al, 2021). These findings encourage us to explore the molecular mechanisms of these genes in BLCA in the future.…”

Advances on the roles of tenascin-C in cancer

“…In gliomas, KO of CD47 induced TNC, which promoted phagocytosis and revealed a poorly understood immune crosstalk that is affected by TNC ( Ma et al, 2019 ). Investigating gene expression patterns revealed that tumors with host-derived TNC upregulated several genes associated with antigen processing and presentation, shedding light on a potential, but as yet poorly understood, DAMP function of TNC in cancer ( Deligne et al, 2020 ; Spenlé et al, 2021 ; Murdamoothoo et al, 2021 ). The balance between pro- and anti-tumorigenic effects of TNC on immune surveillance might regulate whether a tumor thrives or regresses ( Fig.…”