Rationale for investigating efficacy of multiple ICB antibodies originate from clinical studies in melanoma demonstrating higher efficacy of combination of anti-CTLA4 and anti-PD1 versus anti-CTLA-4 (165, 166) or either agent alone in PD-L1-negative patients (166), the limiting factor being however increased toxicity as treatments are combined. The gene discussed is CTLA4; the disease is melanoma.