Control of minimal residual cancer by low dose ipilimumab activating autologous anti-tumor immunity

In this perspective article, we address the controversy regarding the safety-efficacy issue in ipilimumab trials. While the CTLA-4 blockade interrupted T-cell pathways responsible for immune down-regulation and mediated regression of established malignant tumors in a minority of patients, this has to be weighed against the immune related adverse events (irAEs) suffered by the majority. Based on two groundbreaking but neglected proof-of-principle papers that demonstrated augmented graft-vs.-malignancy (GVM) effect that reversed the relapse of malignancy without worsening the graft-vs.-host disease (GVHD) by a CTLA-4 blockade, here we suggest a therapeutic paradigm shift, which may help break the impasse and resolve this timely issue in oncology.