Immune checkpoint therapies targeting inhibitory receptors on T cells have revolutionized the treatment of melanoma by overcoming tumor immune suppression.[48] However, their efficacy is limited to a subset of patients with pre‐existing CD8+ T cells in the tumor.[49] We, therefore, investigated if the antitumor efficacy of C5‐PE38 can be augmented with PD‐1 blockade. The gene discussed is CD8A; the disease is melanoma.