Preclinical studies demonstrate that TIGIT, LAG-3, and CTLA-4 contribute to T-cell exhaustion through distinct mechanisms, and their co-blockade enhances CD8+ T-cell responses, reduces Treg-mediated immunosuppression, and delays tumor growth in murine models (Qin et al., 2019; Huang et al., 2017). The gene discussed is CD8A; the disease is neoplasm.