Beyond the PD-1/PD-L1 and CTLA-4 pathways, other co-inhibitory receptors - including TIM-3, LAG-3, and T cell immune receptor with Ig and ITIM domains (TIGIT; Ig: immunoglobulin domain, ITIM: immunoreceptor tyrosine-based inhibitory motif), which are expressed on tumor-infiltrating lymphocytes - have emerged as promising next-generation targets for reversing T-cell exhaustion and reinvigorating anti-tumor immune responses. The gene discussed is CD274; the disease is neoplasm.