Genomics-based immuno-oncology: bridging the gap between immunology and tumor biology

Abstract

Abstract The first hypotheses about how the immune system affects cancers were proposed in the early 20th century. These early concepts about cancer immunosurveillance were further developed in the decades that followed, but a detailed understanding of cancer immunity remained elusive. It was only recently, through the advent of high-throughput technologies, that scientists gained the ability to profile tumors with a resolution that allowed for granular assessment of both tumor cells and the tumor microenvironment. The advent of immune checkpoint inhibitors (ICIs), which have proven to be effective cancer therapies in many malignancies, has spawned great interest in developing biomarkers for efficacy, an endeavor that highlighted the value of dissecting tumor immunity using large-scale methods. Response to ICI therapy has been shown to be a highly complex process, where the dynamics of tumor and immune cells is key to success. The need to understand the biologic mechanisms at the tumor–immune interface has given rise to the field of cancer immunogenomics, a discipline that aims to bridge the gap between cancer genomics and classical immunology. We provide a broad overview of this emerging branch of translational science, summarizing common platforms used and recent discoveries in the field, which are having direct clinical implications. Our discussion will be centered around the genetic foundations governing tumor immunity and molecular determinants associated with clinical benefit from ICI therapy. We emphasize the importance of molecular diversity as a driver of anti-tumor immunity and discuss how these factors can be probed using genomic approaches.