Impact of cancer evolution on immune surveillance and checkpoint inhibitor response

Intratumour heterogeneity (ITH) is pervasive across all cancers studied and may provide the evolving tumour multiple routes to escape immune surveillance. Immune checkpoint inhibitors (CPIs) are rapidly becoming standard of care for many cancers. Here, we discuss recent work investigating the influence of ITH on patient response to immune checkpoint inhibitor (CPI) therapy. At its simplest, ITH may confound the diagnostic ac-curacy of predictive biomarkers used to stratify patients for CPI therapy. Furthermore, ITH is fuelled by mechanisms of genetic instability that can both engage immune surveillance and drive immune evasion. A greater appreciation of the interplay between ITH and the immune system may hold the key to increasing the proportion of patients experiencing durable responses from CPI therapy.

Automated summary

Intratumour heterogeneity (ITH) can affect the response of patients to immune checkpoint inhibitor (CPI) therapy, confounding the accuracy of predictive biomarkers and playing a role in both immune surveillance and immune evasion. A deeper understanding of the interaction between ITH and the immune system can potentially increase the proportion of patients experiencing durable responses from CPI therapy.