Abstract IA26: Genomic correlates of response and resistance to immune checkpoint blockade

The rise of multiple immunotherapies, such as immune checkpoint blockade, has significantly improved outcomes for multiple patient populations, including melanoma, lung adenocarcinoma, and urothelial cancers, among others. In parallel, the expansion of precision cancer medicine through robust interrogation of cancer genomes at the point of care has enhanced patient stratification for multiple treatment selection strategies and cancer types. The intersection of clinical cancer genomics and immuno-oncology has created an opportunity to learn how the tumor and germline genomes, along with transcriptomic measurements of the immune microenvironment, impact clinical immune checkpoint blockade response. Here, we describe the current landscape of tumor and microenvironmental genomic correlates of immune checkpoint blockade across cancer subtypes, and examine how emerging genomic studies of immunotherapy responders and non-responders may inform patient selection strategies for clinical trial design in these diverse clinical settings. We explore how these approaches, paired with emerging computational biology methodology, may also enable discovery of new mechanisms of selective treatment response. Finally, we examine emerging genomic data on clinical resistance to immunotherapies, from both signaling pathway and neoantigen evolution perspectives, and discuss the implications for combination treatment strategies. Overall, the convergence of comprehensive clinical genomics and immuno-oncology treatment strategies may inform precision medicine for immunotherapies across cancer types. Citation Format: Eliezer M. Van Allen. Genomic correlates of response and resistance to immune checkpoint blockade. [abstract]. In: Proceedings of the AACR Special Conference on Tumor Immunology and Immunotherapy; 2016 Oct 20-23; Boston, MA. Philadelphia (PA): AACR; Cancer Immunol Res 2017;5(3 Suppl):Abstract nr IA26.