Targeting co-stimulatory molecules that belong to the tumor necrosis factor receptor (TNFR) family such as OX40, ICOS, GITR, CD40L, and 4-1BB with agonist antibodies have been found to improve T cell function, with favorable outcomes in some cancer patients [reviewed in Moran et al. (33)]. This evidence concerns the gene TNFRSF4 and cancer.