Immunotherapeutic strategies beyond the PD-1/PD-L1 pathway in head and neck squamous cell carcinoma – A scoping review on current developments in agents targeting TIM-3, TIGIT, LAG-3, and VISTA

Head and neck squamous cell carcinoma (HNSCC) poses a considerable challenge due to its high incidence and mortality rates. Immunotherapy targeting PD-(L)1 emerges as a promising approach for HNSCC, as it has the potential to trigger a broad and long-lasting anti-tumor response. Nevertheless, the effectiveness of immunotherapy encounters hurdles, and only a small proportion of patients benefit, with many eventually experiencing relapse. Consequently, there is a pursuit of strategies to enhance overall treatment outcomes. Understanding the mechanisms driving resistance to PD-(L)1 inhibition and devising strategies to overcome these challenges are vital for advancing more effective treatments. Furthermore, gaining insights into the mechanisms of action and safety profiles of novel combination therapies is critical for their successful adoption in clinical practice. As a result, current research is dedicated to investigating various immunotherapeutic agents beyond the PD-1/PD-L1 axis. This review offers a comprehensive overview of the existing immunotherapy strategies in HNSCC with a focus on TIM-3, TIGIT, LAG-3, and VISTA. The aim is to lay a strong foundation for the continual advancement of therapies for HNSCC.