Cancer of the head and neck (HNC) is a heterogeneous disease of the upper aerodigestive tract, encompassing distinct histologic types, different anatomic sites, and human papillomavirus (HPV)-positive as well as HPV-negative
cancers. Advanced/recurrent HNCs have poor prognosis with low survival rates.
Tumor-mediated inhibition of antitumor immune responses and a high mutational burden are common features of HNCs. Both are responsible for the successful escape of these
tumors from the host immune system. HNCs evolve numerous mechanisms of evasion from immune destruction. These mechanisms are linked to genetic aberrations, so that HNCs with a high mutational load are also highly immunosuppressive. The tumor microenvironment of these
cancers is populated by immune cells that are dysfunctional, inhibitory
cytokines, and exosomes carrying suppressive
ligands. Dysfunctional immune cells in patients with recurrent/metastatic HNC can be made effective by the delivery of
immunotherapies in combination with conventional treatments. With many promising immune-based strategies available, the future of immune
therapies in HNC is encouraging, especially as methods for genetic profiling and mapping the immune landscape of the
tumor are being integrated into a personalized approach. Efficiency of immune
therapies is expected to rapidly improve with the possibility for patients' selection based on personal immunogenomic profiles. Noninvasive
biomarkers of response to
therapy will be emerging as a better understanding of the various molecular signals co-opted by the
tumors is gained. The emerging role of
immunotherapy as a potentially beneficial addition to standard treatments for recurrent/metastatic HNC offers hope to the patients for whom no other therapeutic options exist. Clin
Cancer Res; 24(1); 6-13. ©2017 AACR.