Recent evidence has indicated that, rather than fully exhausted CD8+ T cells, preexhausted (progenitor exhausted) CD8+ T cells with proliferative capacity, such as CD8+ T cells positive for PD-1 and T cell factor 1 (TCF1), are the major effector cells attacking cancer cells during PD-1 blockade therapy (25, 28–33). The gene discussed is CD8A; the disease is cancer.