Immunotherapy in Head and Neck Cancer When, How, and Why?

Abstract

Head and neck cancer (HNC) is one of the most common cancers worldwide. Alcohol and tobacco consumption, besides viral infections, are the main risk factors associated with this cancer. When diagnosed in advanced stages, HNC patients present a higher probability of recurrence or metastasising. The complexity of therapeutic options and post-treatment surveillance is associated with poor prognosis and reduced overall survival (OS). This review aims to explore immunotherapy (immune checkpoint inhibitors (ICI), therapeutic vaccines, and oncolytic viruses) in HNC patients’ treatment, and to explore when, how, and why patients can benefit from it. The monotherapy with ICI or in combination with chemotherapy (QT) shows the most promising results. Compared to standard therapy, ICI are able to increase OS and patients’ quality of life. QT in combination with ICI demonstrates significant response rates and considerable long-term clinical benefits. However, the toxicity associated with this approach is still a hurdle to overcome. In parallel, the therapeutic vaccines directed to the Human Papilloma Virus are also efficient in increasing the antitumour response, inducing cellular and humoral immunity. Although these results demonstrate clinical benefits compared to standard therapy, it is also important to unravel the resistance mechanisms in order to predict the clinical benefit of immunotherapy.

Systemic Inflammatory Disorders, Immunosuppressive Treatment and Increase Risk of Head and Neck Cancers—A Narrative Review of Potential Physiopathological and Biological Mechanisms

“…However, chronic inflammation and immunological dysregulation may contribute to a slightly elevated risk as we will address in more detail. It is also important to highlight that, contrary to what we can observe in cell-mediated inflammatory diseases, the effectiveness of immunotherapy in treating HNC associated with humoral inflammatory diseases is still not well established [35]. Since these diseases involve complex immune system abnormalities, their interaction with immunotherapy agents may differ from that of cell-mediated diseases.…”

Recent advances in head and neck surgical oncology

“…Pembrolizumab, a PD-1 monoclonal antibody, made groundbreaking strides as the first immunotherapy for recurrent or metastatic head and neck squamous cell carcinoma. 44 The KEYNOTE studies, spanning Phases I-III, meticulously assessed its efficacy and safety. [45][46][47] Harrington et al 48 recently reported updated results from the Phase III KEYNOTE-048 study, showing that even after a 4-year follow-up, first-line pembrolizumab and pembrolizumab-chemotherapy still provided better survival outcomes compared to cetuximab-chemotherapy in recurrent/metastatic head and neck squamous cell carcinoma.…”

“…In such circumstances, immunotherapy is steadily earning recognition as a preferred choice for treatment. Pembrolizumab, a PD‐1 monoclonal antibody, made groundbreaking strides as the first immunotherapy for recurrent or metastatic head and neck squamous cell carcinoma 44 . The KEYNOTE studies, spanning Phases I–III, meticulously assessed its efficacy and safety 45–47 .…”

Immune checkpoint CD161/LLT1‐associated immunological landscape and diagnostic value in oral squamous cell carcinoma

“…However, traditional treatments can cause significant side effects and may not be effective for all patients [ 3 , 4 ]. Recently, immunotherapy, including immune checkpoint inhibitors, has emerged as a promising treatment option for oral cancer [ 5 , 6 ]. Immune checkpoint inhibitors, such as those that target programmed cell death protein 1 (PD‐1), have shown encouraging results since they were approved in 2014 for the treatment of various solid tumors [ 7 ].…”