Lastly, CD73 catalyzes the hydrolysis of AMP into phosphate and adenosine that suppresses the TME, thus establishing a “purinergic milieu.” On the other hand, the CD39/CD73/adenosine signaling establishes an immunosuppressive melanoma microenvironment restraining both innate and adaptive anti-tumor immunity through dedicated adenosine receptors, namely A1, A2A, A2B, and A3 (87). Here, ENTPD1 is linked to melanoma.