Immunotherapy Approaches Beyond PD-1 Inhibition: the Future of Cellular Therapy for Head and Neck Squamous Cell Carcinoma

In a span of a few years, the surprising early successes of programmed cell death 1 (PD-1) inhibitors across a vast range of tumor types have transformed our understanding of cancer immunogenicity and provided proof of principle that T cells, if manipulated, can mediate meaningful tumor regression. In head and neck cancer, only a minority of patients respond to PD-1 therapy, but these small outcomes have fueled the enthusiasm for the next generation of immunotherapy—adoptive cell therapy—which employs recent advances in genetic engineering and cell culturing methods to generate T cells with enhanced anti-tumor efficacy for infusion back into the patient. Head and neck cancer is comprised of biologically distinct cancers, HPV-positive and HPV-negative, and the clinical responses to PD-1 inhibitors in both HPV-positive and HPV-negative head and neck patients have showcased better than any other cancer type that there are distinct pathways to immunogenicity that may lend themselves to different therapeutic approaches. Thus, head and neck cancer is uniquely poised to benefit from the personalized approach of adoptive cell therapy as well as provide a valuable platform to explore contrasting T cell modalities. In this article, we will review the growing portfolio of trials of adoptive cell therapies in head and neck cancer and discuss the future directions of this emerging new field.