Agonists to tumor necrosis factor receptor family members such as anti-4-1BB have shown clinical activity in early clinical trials, and there is ample preclinical evidence that T-cell co-stimulation via 4-1BB can induce immune-mediated rejection of tumors.10, 11 All of these agents are currently in clinical trials for a number of malignancies and have led to immunotherapy being dubbed the ‘cancer breakthrough of the year' in 2013.12 This evidence concerns the gene TNFRSF9 and cancer.