This enhanced therapeutic efficacy demonstrated with combinatorial PD-1 and CTLA-4/TIM-3/TIGIT blockade demonstrates that immune checkpoints which function in distinct yet synergistic stages in the immune response, namely the priming (CTLA-4/TIM-3/TIGIT) and effector (PD-1) phases of the adaptive immune response, can synergise to enhance anti-tumour immunity. This evidence concerns the gene CTLA4 and neoplasm.