Immune checkpoint blockade (ICB) Abs that target programmed death 1 (PD-1) and cytotoxic T lymphocyte–associated protein 4 (CTLA-4), which are focused on activating and mobilizing the body’s immune system to eradicate malignant cells, have provided therapeutic benefits to patients with multiple malignancies, including melanoma, but a significant proportion of patients fail to benefit from such immunotherapies (1). The gene discussed is CTLA4; the disease is melanoma.