In contrast, CD226 is down-regulated on tumor-infiltrating Treg, and a high TIGIT/CD226 expression ratio on tumor-infiltrating Tregs correlates with high Treg frequencies in tumors and poor clinical outcome in melanoma patients treated with anti-PD-1 and/or anti-CTLA4 immune checkpoint blockade, suggesting that the TIGIT/CD226 ratio in Tregs is a marker of Treg stability (76). This evidence concerns the gene CTLA4 and neoplasm.