Immunogenomic precision medicine: a personalized approach based on immunogenomic cancer evolution.

Abstract

Cancer progression can be understood as a process of diversification and selection (the evolutionary theory of cancer). The immune system also plays a critical role in this process of diversification and selection. The cancer immunoediting hypothesis provides a partial explanation of this evolutionary process; immune-evading cancer clones with genomic and/or epigenomic alterations are selected under the pressure of immune surveillance and can become equipped with multiple immunosuppressive mechanisms, leading to the development of clinically apparent cancers. Indeed, inflammatory cancers equip immunosuppressive mechanisms in response to the pressure of the immune system. However, recent studies focusing on human cancers have revealed that certain non-inflammatory cancers, which often harbor a single driver oncogenic mutation, are equipped with immunosuppressive machinery sufficient to evade immune surveillance at the time of malignant transformation. The sequential model of the cancer immunoediting hypothesis is inadequate to explain the development of these non-inflammatory cancers, highlighting the need for a novel concept that can explain their co-evolutionary processes. Moreover, inhibition of oncogenic signaling by specific driver oncogenes has been shown not only to kill cancer cells but also to augment antitumor immunity, suggesting the potential for the advent of molecularly targeted reagents with a variety of immunomodulatory functions from the perspective of personalized therapies. Here, we discuss the processes by which cancer cells and the immune system co-evolve to establish clinically apparent cancers, thereby introducing a new concept of 'immunogenomic cancer evolution', that provides a rationale for the potential of personalized 'immunogenomic cancer precision medicine'.