Furthermore, downregulation of CD226 is often accompanied by upregulation of coinhibitory immune checkpoint receptors such as TIGIT, PD-1, Tim-3, and LAG-3 in CD8+TILs from patients with RCC, CRC, NSCLC, squamous cell carcinoma (SCC), and melanoma, which can be considered phenotypic characteristics of exhausted T cells9,55,64. This evidence concerns the gene CD226 and melanoma.