A review on the advances and challenges of immunotherapy for head and neck cancer.

Head and neck cancer (HNC), which includes lip and oral cavity, larynx, nasopharynx, oropharynx, and hypopharynx malignancies, is one of the most common cancers worldwide. Due to the interaction of tumor cells with immune cells in the tumor microenvironment, immunotherapy of HNCs, along with traditional treatments such as chemotherapy, radiotherapy, and surgery, has attracted much attention. Four main immunotherapy strategies in HNCs have been developed, including oncolytic viruses, monoclonal antibodies, chimeric antigen receptor T cells (CAR-T cells), and therapeutic vaccines. Oncorine (H101), an approved oncolytic adenovirus in China, is the pioneer of immunotherapy for the treatment of HNCs. Pembrolizumab and nivolumab are mAbs against PD-L1 that have been approved for recurrent and metastatic HNC patients. To date, several clinical trials using immunotherapy agents and their combination are under investigation. In this review, we summarize current the interaction of tumor cells with immune cells in the tumor microenvironment of HNCs, the main strategies that have been applied for immunotherapy of HNCs, obstacles that hinder the success of immunotherapies in patients with HNCs, as well as solutions for overcoming the challenges to enhance the response of HNCs to immunotherapies.