CD274 and neoplasm: CTLA-4 inhibition drives immune-suppression in tumor-antigen presenting cells and T-regs, while PD-1/PD-L1 blockade predominantly downregulates the effectiveness of the cytotoxic CD8+ T cell response.13 Unfortunately, combinations of ICI plus TKI, such as atezolizumab plus cabozantinib or pembrolizumab plus lenvatinib, did not statistically improve OS compared to TKI monotherapy in phase III RCTs.14,15 Overall, compared to ICI monotherapies, ICI-based doublets are associated with improved outcomes, and this is probably related to the added benefit of each component.