CD39 (ENTPD1) is a cell-surface ectonucleotidases that contributes to regulate TIME and immunotherapy response through the hydrolysis of extracellular ATP and ADP, leading to immunosuppressant adenosine generation.[14–16] CD39+ Tregs enhance immunosuppressive activity by promoting immune evasion in malignancies such as non-small cell lung cancer and colon adenocarcinoma.[17] The observed association between CD3 (T cell co-receptor) expression and HSIL risk suggests that TCR activation in CD39+ Tregs may amplify their adenosine-mediated immunosuppressive capacity. This evidence concerns the gene ENTPD1 and colon adenocarcinoma.