Likewise, single agent IL-15 agonists have not been very successful in treating human tumors, and the initial trials of single-chain IL-15 in high doses required to induce immune changes resulted in dose-limiting toxicities with no clinical response (42); the consensus is that maximal efficacy of IL-15 will require combinations with other anti-cancer agents, such as the tumor specific monoclonal antibodies CTLA-4 and PD-L1 (6, 43). This evidence concerns the gene CD274 and cancer.