Immunotherapies and Future Combination Strategies for Head and Neck Squamous Cell Carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is often diagnosed at an advanced stage and has a dismal prognosis. Nearly 10 years after the approval of cetuximab, anti-PD1/PD-L1 checkpoint inhibitors are the first drugs that have shown any survival benefit for the treatment on platinum-refractory recurrent/metastatic (R/M) HNSCC. Furthermore, checkpoint inhibitors are better tolerated than chemotherapy. The state of the art in the treatment of R/M HNSCC is changing, thanks to improved results for checkpoint inhibitors. Results for these treatments are also awaited in curative settings and for locally advanced HNSCC. Unfortunately, the response rate of immunotherapy is low. Therefore, the identification of predictive biomarkers of response and resistance to anti-PD1/PD-L1 is a key point for better selecting patients that would benefit the most from immunotherapy. Furthermore, the combination of checkpoint inhibitors with various agents is being currently evaluated to improve the response rate, prolong response duration, and even increase the chances for a cure. In this review, we summarize the most important results regarding immune targeting agents for HNSCC, predictive biomarkers for resistance to immune therapies, and future perspectives.

On-treatment immune prognostic score for patients with relapsed and/or metastatic head and neck squamous cell carcinoma treated with immunotherapy

“…3 Other trials of immune checkpoint inhibitors (ICIs) or combinations with other immune-stimulatory drugs are also tracking first-line and secondline benefit. 4 Although ICIs present a promising new opportunity, objective responses remain around 20% in first-line and secondline patients with R/M HNSCC unselected for tumor PD-L1 expression. In addition, despite data showing that PD-L1 correlates with better efficacy of ICIs, no other reliable biomarker for effectively selecting optimally responsive patients has been identified as yet.…”

The miR‑136‑5p/ROCK1 axis suppresses invasion and migration, and enhances cisplatin sensitivity in head and neck cancer cells

“…Overall, the 5-year survival rate for patients with HNSCC has remained at 40-60% and is accompanied by a relatively poor prognosis (1,4,5). Laryngeal squamous cell carcinoma (LSCC) and hypopharyngeal squamous cell carcinoma (HPSCC) are two types of HNSCC with high incidence rates and a relatively poor prognosis following treatment (6)(7)(8). Although multiple proteins and pathways have been shown to be associated with the development of LSCC and HPSCC, the exact molecular mechanisms of action and potential therapeutic targets affecting proliferation and migration remain to be elucidated (9).…”

ECM Remodeling in Squamous Cell Carcinoma of the Aerodigestive Tract: Pathways for Cancer Dissemination and Emerging Biomarkers

“…A combination with preoperative neoadjuvant or postoperative adjuvant radiotherapy and chemotherapy has slightly improved patient prognosis [ 17 , 18 , 19 ]. The use of immunotherapy in combination with conventional chemotherapy has recently been considered as a possibility to significantly improve the outcome of these patients [ 12 , 20 ]. Despite the fact that these therapeutic approaches have given some benefits, the overall outcome of UADT SCC patients is still unsatisfactory.…”