Next-generation immunotherapies for head and neck squamous cell carcinoma: targeting novel immune checkpoints

The purpose of this review is to explore eight novel immune checkpoints (PD-L2, B7-H3, VISTA, BTLA, TIM-3, LAG-3, TIGIT and GITR) in head and neck squamous cell carcinoma (HNSCC), including their biological properties, therapeutic potential and the possibility of combining them with other immune checkpoints (ICs) or emerging biotechnological approaches such as nanomaterials, oncolytic viruses (OVs) and tumour vaccines, with the aim of providing new treatment directions for HNSCC.

We conducted a review and analysis of numerous studies in the past 5 years to understand the expression patterns, roles and the current state of related therapies for these eight novel ICs in HNSCC. We also examined the synergistic effects of combining these ICs with immune checkpoint inhibitors (ICIs), nanomaterials, OVs and tumour vaccines.

These novel ICs show unique expression and functions in HNSCC, offering new targets for overcoming tumour immune heterogeneity and resistance. Therapies targeting these ICs, such as monoclonal antibodies and small molecule inhibitors, have shown potential in preclinical studies. Moreover, combining these ICs with ICIs, nanomaterials, OVs and tumour vaccines has demonstrated enhanced antitumour effects, indicating broad application prospects.

The eight novel ICs and their integration with emerging biotechnological approaches provide new hope for HNSCC treatment. Further research is needed to clarify the mechanisms of these novel ICs and optimize combination strategies to improve treatment precision and efficacy for HNSCC patients.