A prime example of enhanced efficacy with combination therapy is the use of antibodies that block two key immune checkpoints, CTLA-4 and PD-1, which results in significantly higher response rates to therapy and improved clinical outcomes as compared to monotherapy, and this combination was recently FDA-approved for patients with metastatic melanoma [24, 25, 27, 137]. This evidence concerns the gene CTLA4 and metastatic melanoma.