Targeting CD39 offers the theoretical potential to impact anti-tumor immunity in a twofold fashion: firstly, decreasing the extracellular adenosine reverses the adenosine receptor-mediated broadly and long term immune-suppressive TME; secondly, preventing the conversion of ATP to AMP results in the accumulation of eATP, a pro-inflammatory danger signal which will be available at relatively high concentration and thus stimulates immune cells in the TME [95–99]. This evidence concerns the gene ENTPD1 and neoplasm.