An important limitation to ICB is the occurrence of serious adverse events (SAEs) a large proportion of treated patients suffers from. Data obtained from clinical trials show that approximately 60% of stage IV and 90% of stage III melanoma patients treated with dual CTLA-4/PD-1 blockade experiences grade 3/4 SAEs. There is consensus among clinical oncologists that many patients are currently overtreated with ICB, which is likely to explain part of the toxicity, however, tools are lacking to drive patient specific dosing of these drugs. The observation that SAEs occur more frequently in patients with a lower disease stage strongly suggests that the occurrence of toxicity is related to general immune function, i.e. immunocompetence, of patients. In support of this model, prior work has provided evidence for systemic immunosuppression in cancer patients based on analyses of e.g. dendritic cells in peripheral blood. Furthermore, this immunosuppression was shown to increase with disease progression, demonstrating that tumor-unrelated immune activity appears to be disease stage dependent. Based on these data, ‘bystander’ T cells are also expected to be influenced by disease stage, and importantly a large part of the observed immune related SAEs to ICB are T cell mediated. We are therefore examining the relationship between the activity and state of such bystander T cells with disease stage and the toxicity to ICB. If there is a correlation between T cell activity/state and toxicity to ICB, such knowledge could be utilized to develop a tool to predict the risk of potential toxicity for each individual and adjust the dosing schedule per patient to ensure treatment can be given in a safer manner.