Tumor microenvironment and immune-related therapies of head and neck squamous cell carcinoma

Head and neck squamous cell carcinomas (HNSCCs) are a type of common malignant tumor, mainlymanifesting as oropharyngeal, oral cavity, laryngopharyngeal, hypopharyngeal, and laryngeal cancers. These highly aggressive malignant tumors reportedly affect more than 830,000 patients worldwide every year. Currently, the main treatments for HNSCC include surgery, radiotherapy, chemotherapy, and immunotherapy, as well as combination therapy. However, the overall 5-year survival rate of HNSCC has remained 50%, and it has not significantly improved in the past 10 years. Previous studies have shown that the tumor microenvironment (TME) plays a crucial role in the recurrence, metastasis, and drug resistance of patients with HNSCC. In this review, we summarize the role of anti-tumor and pro-tumor immune cells, as well as extracellular components in the TME of HNSCC. We also discuss classical HNSCC immunotherapy and highlight examples of clinical trials using CTLA-4 inhibitors and programmed cell death 1 (PD1)/programmed cell death ligand 1 (PD-L1)-related combination therapies. We also outline somemolecules in the TME known to regulate immunosuppressive cells. Furthermore, the role and underlying mechanism of radiation therapy on the TME, immune cells, and immune response are discussed.