Orthotopic model of tongue cancer for the study of head and neck squamous cell carcinoma in mice

Head and neck squamous cell carcinoma (HNSCC) is among the most prevalent human malignancies globally, with approximately 887,000 new cases diagnosed each year. Currently, the standard treatment for HNSCC involves surgery, followed by radiotherapy, chemotherapy and immunotherapy. However, despite these available treatments, the survival rate of patients with HNSCC remains low. A key factor in the development of HNSCC is genomic instability, which significantly influences several phases of the disease such as initiation and progression. Given the complexity of HNSCC, preclinical models are essential for exploring the mechanisms driving HNSCC progression, at the (epi)genetic (e.g., DNA mutations, histone modifications), cellular (e.g., resistance to cell death, autophagy) and histological (e.g., cancer-immunity cycle) levels. Moreover, such a model is precious for developing new therapies. In this context, we provide a comprehensive protocol outlining the steps required to establish a syngeneic orthotopic tongue mouse model, including cell preparation and injection steps. By implanting cells in their natural anatomical location within immunocompetent mice, this model allows to investigate interactions between the tumor and surrounding tissues, which can significantly influence tumor growth.