FIGURE 1.

Persistent mutations represent an uneditable set within the overall TMB that may drive immunologic tumour control and sustained clinical therapeutic responses. Persistent mutations in cancer cells are resistant to tumour immune‐editing during the natural course of tumour evolution and contribute to sustained immunologic tumour control. During ICB treatment, tumours with high persistent mutation burden are more likely to regress due to their inability to evade immune recognition by mutation loss, resulting in sustained therapeutic response and favourable outcome. Conversely, loss‐prone mutations and their associated neoantigens are more likely to be eliminated in the process of tumour evolution. Therefore, tumours with predominantly loss‐prone mutations can undergo immune escape leading to disease progression in the context of therapy.