Checkpoint targeting immunotherapies have revolutionized the treatment of patients with lung cancer, melanoma and several other tumour types. Recent results demonstrate that the presence of high cancer mutation and neo-antigen loads is critical for treatment success, indicating that the T cells that are unleashed by immunotherapy mainly recognize neo-antigens.
At the same time, many solid cancers are genetically highly heterogeneous, leading to variable neo-antigen profiles in different tumour subclones and enabling tumours to evolve under selection pressure. I will discuss current data on genetic heterogeneity and cancer evolution and their impact on immunotherapy responses and resistance.