Neoantigen-Reactive T Cells: The Driving Force behind Successful Melanoma Immunotherapy

SIMPLE SUMMARY: Cancer immunotherapy is a revolutionary type of cancer therapy. It uses the patient’s own immune system to fight and potentially cure cancer. The first major breakthrough of immunotherapy came from successful clinical trials for melanoma treatments. Since then, researchers have focused on understanding the science behind immunotherapy, so that patients with other types of cancer may also benefit. One of the major findings is that the T cells in melanoma patients may recognize a specific type of tumor antigen, called neoantigens, and then kill tumor cells that present these neoantigens. The neoantigens mainly arise from the DNA mutations found in tumor cells. These mutations are translated into mutated proteins that are then distinguished by T cells. In this article, we discuss the critical role of T cells in immunotherapy, as well as the clinical trials that shaped the treatments for melanoma. ABSTRACT: Patients with metastatic cutaneous melanoma have experienced significant clinical responses after checkpoint blockade immunotherapy or adoptive cell therapy. Neoantigens are mutated proteins that arise from tumor-specific mutations. It is hypothesized that the neoantigen recognition by T cells is the critical step for T-cell-mediated anti-tumor responses and subsequent tumor regressions. In addition to describing neoantigens, we review the sentinel and ongoing clinical trials that are helping to shape the current treatments for patients with cutaneous melanoma. We also present the existing evidence that establishes the correlations between neoantigen-reactive T cells and clinical responses in melanoma immunotherapy.