Biological mechanisms of immune escape and implications for immunotherapy in head and neck squamous cell carcinoma

Abstract

Head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with high morbidity and mortality. Despite advances in cytotoxic therapies and surgical techniques, overall survival (OS) has not improved over the past few decades. This emphasises the need for intense investigation into novel therapies with good tumour control and minimal toxicity. Cancer immunotherapy has led this endeavour, attempting to improve tumour recognition and expand immune responses against tumour cells. While various forms of HNSCC immunotherapy are in preclinical trials, the most promising direction thus far has been with monoclonal antibodies (mAbs), targeting growth factor and immune checkpoint receptors. Preclinical and early phase trials have shown unprecedented efficacy with minimal adverse effects. This article will review biological mechanisms of immune escape and implications for immunotherapy in HNSCC.

Cisplatin Alters Antitumor Immunity and Synergizes with PD-1/PD-L1 Inhibition in Head and Neck Squamous Cell Carcinoma

“…Head and neck squamous cell carcinoma (HNSCC), the sixth most common cancer type worldwide, is an aggressive malignancy with little improvement in overall survival during the past few decades (1). Clinical trials have focused on improving survival for patients with HNSCC related to carcinogen exposure, who have a relatively poor prognosis, and reducing treatment-related toxicities in patients with human papillomavirus (HPV)-associated HSNCC, which portends a relatively favorable prognosis (2).…”

Tongue cancer epidemiology in Brazil: incidence, morbidity and mortality

“…Cases of SCC of the head and neck present a 5‐year survival rate of only 40%‐60% in the last 50 years, despite advances in surgical techniques, radiotherapy, chemotherapy, and combined therapies . The incidence of this type of cancer, especially of cancer of the mobile tongue and oropharynx, has increased significantly in the United States between 1973 and 2012, in younger patients of both sexes …”

“…[4][5][6] Cases of SCC of the head and neck present a 5-year survival rate of only 40%-60% in the last 50 years, despite advances in surgical techniques, radiotherapy, chemotherapy, and combined therapies. 7 The incidence of this type of cancer, especially of cancer of the mobile tongue and oropharynx, has increased significantly in the United States between 1973 and 2012, in younger patients of both sexes. 8 In the 2017 World Health Organization classification of head and neck tumors, oral cancer is enclosed together with mobile tongue, whereas oropharynx and base of the tongue cancers are depicted in an independent chapter recognizing the uniqueness of oropharyngeal and base of the tongue tumors.…”

The promise of immunotherapy in the treatment of young adults with oral tongue cancer

“…TGF‐β is associated with suppressed T and NK cell activation as well as stimulating differentiation of immunosuppressive Treg cells . In contrast to immunosuppressive Treg cells, CD8 cytotoxic T lymphocytes are considered to be the critical immune cell involved in mounting a successful host antitumor response, and considerable data support the notion that higher infiltration of CD8 T cells into the TME are associated with improved locoregional control and overall survival in patients with head and neck cancer across multiple subsites …”