Squamous cell carcinoma is the most frequently occurring malignant tumor in the head and neck. More than 90% of squamous cell carcinoma of the head and neck (SCCHN) originate from the mucosal linings of the oral cavity, pharynx, or larynx. The estimated worldwide incidence of SCCHN in 2012 was approximately 686,000, with approximately 375,000 deaths.1 Oral cavity cancer in particular is a significant and growing problem in many parts of the world, with an estimated annual incidence of around 263,000.2
Up to 50% of patients with head and neck cancer will relapse at a local or distant site within 2 years.3 A patient’s survival is largely dependent on the type and stage of disease. The relative 5-year survival rates for head and neck cancers are about 50% and have not changed much in the last 50 years.4 Recurrent disease is generally treated with radiation therapy, chemotherapy, biological therapy, or a combination of these modalities.5,6 Recurrence and death, however, are closely correlated, with median survival durations of only 3 to 9 months. Successfully treated patients may still have to cope with consequences of their treatment that affect appearance, function, and quality of life. Clearly, better therapies are needed.
Patients with SCCHN are consistently found to have disordered immune function at the time of presentation. SCCHN patients have immunological deficiencies of T-cell anergy and defective monocyte/macrophage function.7,8 High PD-L1 expression on SCCHN cells contributes to immunosuppression through multiple proposed mechanisms including inhibiting the effects and causing death of anticancer T cells.9
The cumulative result of the various immune defects and immunosuppressive mechanisms in SCCHN is7,8,10: