Several groups, including our own, have reported multiple mechanisms for low antitumor CD8+ T cell infiltration in the TME, such as upregulation of WNT/β-catenin (5, 6), activation of oncogenic pathways due to gene alterations (7–9), and systemic immunosuppression or cytotoxic T cell depletion caused by tumor localization or the metabolic environment in specific organs (10–13), and targeting these mechanisms significantly improved the therapeutic efficacy of PD-1–blocking treatment in preclinical models. The gene discussed is PDCD1; the disease is neoplasm.