Molecular insights into immune evasion in head and neck squamous cell carcinomas: Toward a promising treatment strategy

Abstract

Head and neck squamous cell carcinoma (HNSCC) is a highly aggressive and devastating disease arising primarily from the mucosal epithelium of the oral cavity, pharynx, and larynx. HNSCC ranks as the sixth most common cancer worldwide, carrying significant morbidity and mortality. HPV-positive HNSCC can be partially prevented with the FDA-approved HPV vaccine and generally exhibits a more favorable prognosis compared to HPV-negative cases. However, effective screening and treatment approaches remain elusive for HPV-negative HNSCC. While precancerous lesions may precede invasive cancer in certain situations, most patients present with advanced disease without prior indication of precancerous conditions. Despite robust immune cell infiltration in HNSCC tumors, the extent and composition of immune infiltration vary widely among patients, and these tumors often evade immune surveillance through diverse mechanisms. Given the heterogeneous nature of HNSCC influenced by anatomical location and etiological factors, precise identification of biomarkers and personalized treatment strategies are imperative. In this study, we aim to explore the possibility of establishing an effective treatment strategy to overcome obstacles to targeted treatment and enable long-term survival through detailed molecular characterization and immune profiling of HNSCC.

Keywords: Cancer-associated fibroblast; HNSCC; Human papillomavirus; Tumor microenvironment; Tumor-associated macrophage.

Figure 1. A summary of the differences in biomarkers and tumor microenvironment (TME) between HPV-positive and HPV-negative HNSCC. This figure was drawn using BioRender.

Figure 2. Schematic illustration of immune evasion in the tumor microenvironment. This figure was drawn using BioRender.