Cancer immune evasion, immunoediting and intratumour heterogeneity

Cancers can avoid immune-mediated elimination by acquiring traits that disrupt antitumour immunity. These mechanisms of immune evasion are selected and reinforced during tumour evolution under immune pressure. Some immunogenic subclones are effectively eliminated by antitumour T cell responses (a process known as immunoediting), which results in a clonally selected tumour. Other cancer cells arise to resist immunoediting, which leads to a tumour that includes several distinct cancer cell populations (referred to as intratumour heterogeneity (ITH)). Tumours with high ITH are associated with poor patient outcomes and a lack of responsiveness to immune checkpoint blockade therapy. In this Review, we discuss the different ways that cancer cells evade the immune system and how these mechanisms impact immunoediting and tumour evolution. We also describe how subclonal antigen presentation in tumours with high ITH can result in immune evasion. Here the authors describe the different ways that cancer cells evade the immune system and how these mechanisms impact immunoediting and tumour clonality. They suggest that in tumours that become highly heterogeneous, presentation of subclonal antigens can result in immune evasion and may explain their poor prognosis and response to immunotherapy.