The key challenge will be to understand resistance mechanisms and to target these, whether by simultaneous targeting of multiple checkpoints such as LAG-3 and TIM-3, or by seeking to interfere with the function of key drivers of tumour immune evasion such as downregulation of MHC class I molecules and upregulation of regulatory T-cell and myeloid-derived suppressor cell function [25]. The gene discussed is HAVCR2; the disease is neoplasm.