The adaptive immune resistance mechanism implies that the blockade of an induced immune-checkpoint protein, such as programmed cell death protein 1 (PD1), as a single intervention will only induce tumour regressions when there is a pre-existing antitumour immune response to be ‘unleashed’ when the pathway is blocked. Multiple interventions, such as vaccines, that activate a de novo antitumour immune response may not induce tumour regressions because tumours respond by upregulating immune-checkpoint ligands. Therefore, combining the two approaches may induce tumour regressions in patients that would not have responded to either treatment alone. PDL1, PD1 ligand 1; TAM, tumour-associated macrophage.