Immunotherapy in head and neck squamous cell carcinoma: An updated review

Squamous cell cancer of the head and neck (HNSCC) is the sixth most common cancer and is associated with significant morbidity and mortality. The tumor microenvironment for HNSCC is a complex interplay of immune cells, stromal cells, and cytokines amongst others. Immunotherapy acts as an effective antineoplastic agent by influencing this complex environment and includes immune checkpoint inhibitors (ICI). ICI have been approved in the frontline setting for recurrent and metastatic (R/M) HNSCC as well as platinum-refractory (second line) R/M HNSCC. However, recent clinical studies highlight that the response to immunotherapy varies, and different ICI, as well as different combination strategies play a crucial role in augmenting the efficacy of immunotherapy. An in-depth analysis and focused study of the immune contexture in patients with HNSCC receiving ICI remains critical. Many novel immunotherapies including CAR-T cell therapy, oncolytic virus therapy, and vaccines are underway. Ongoing trials are testing ICI in the neoadjuvant and adjuvant settings. Furthermore, identifying better biomarkers to target population that benefits from immunotherapy is of paramount importance. Pioneering the optimal combination regimen utilizing new novel immunotherapy has recently become a paradigm shift in the HNSCC treatment landscape. Herein, we summarize the clinical development with all ongoing clinical trials of immunotherapy in HNSCC.