Immunotherapies are not effective in all cancer patients, likely due in part to immunosuppressive networks in advanced tumours. Moynihan et al. found that combination immunotherapy consisting of four components (a tumour antigen-targeting antibody, extended half-life recombinant interleukin-2, a programmed cell death protein 1 (PD1) antibody and a T cell vaccine) could eliminate large tumours in syngeneic mouse tumour models and a genetically engineered mouse model of melanoma. This response required many different immune cell subsets. Importantly, the regimen also seemed to have minimal toxicity.