In one of the first preclinical models of dual therapies targeting the 4-1BB and PD-1 pathways, Xiao et al. demonstrated that systemic administration of soluble PD-1 to inhibit PD-L1 synergized well with implantation of H22 hepatocarinomas transfected with 4-1BBL by increasing anti-tumor cytotoxicity and decreasing tumor burden compared to either monotherapy (184). This evidence concerns the gene CD274 and neoplasm.