Neoantigens in immunotherapy and personalized vaccines: Implications for head and neck squamous cell carcinoma

Abstract

The recent success of immunotherapies has demonstrated the potency of tumor-specific immune cells in mediating tumor rejection and generating durable tumor immunity. Our understanding of the scientific basis of these responses results from the confluence of a better comprehension of the cancer immunoediting process and the revolution in next generation sequencing of cancer genomes. Recent evidence suggests that T cell specificity for cancer cell expressed mutant proteins - termed neoantigens - is an important component of immune mediated tumor rejection. Improved neoantigen prediction algorithms have made it possible to predict and monitor immune responses to checkpoint inhibitors and adoptively transferred autologous lymphocytes and have enabled the development of tumor-specific therapeutic vaccines. Herein, we review the current research on cancer neoantigens in immunotherapies and its implications for the future of head and neck cancer management.

Keywords: Immunogenomics; Neoepitope; Next generation sequencing.

Figure 1

Pathway of class I neoantigen presentation: Mutation-encoded proteins undergo proteolytic degradation in the cytosol and the mutation-derived peptide is loaded onto an MHC class I molecule in the ER with the assistance of TAP. This neoepitope-class I complex undergoes further processing and transport to the cell surface where it is accessible to neoantigen specific CD8+ T-cells (ER: endoplasmic reticulum. TAP: Transporter associated with antigen processing).

Figure 2

Pipeline for clinical neoantigen identification. (A) A tumor biopsy is used for (B) sequencing via WES, WGS or cDNA cap-seq and predicted neoantigens are prioritized based on class I affinity. (C) PBMCs and/or tumor infiltrating lymphocytes are isolated from a tumor biopsy. (D) Peptides and/or tetramers are synthesized and TIL specificity is demonstrated by ELISPOT or (E) tetramer staining.