Neoantigen Controversies

Next-generation sequencing technologies have revolutionized our ability to catalog the landscape of somatic mutations in tumor genomes. These mutations can sometimes create so-called neoantigens, which allow the immune system to detect and eliminate tumor cells. However, efforts that stimulate the immune system to eliminate tumors based on their molecular differences have had less success than has been hoped for, and there are conflicting reports about the role of neoantigens in the success of this approach. Here we review some of the conflicting evidence in the literature and highlight key aspects of the tumor–immune interface that are emerging as major determinants of whether mutation-derived neoantigens will contribute to an immunotherapy response. Accounting for these factors is expected to improve success rates of future immunotherapy approaches.