Perspectives
CD39 has correlation to various immune cells and plays vital roles in multiple physiological and pathological processes. In particular, CD39 is considered to be a new marker of T-cell exhaustion and an immune checkpoint target for cancer treatment. Targeting of both the A2aR and CD73 has been shown to be efficacious in preclinical cancer models. However, unlike treatment targeting the downstream production or function of ADO, inhibition of CD39 not only limits the production of ADO, but also prevents the degradation of eATP. So CD39 is uniquely positioned in ATP-adenosine axis. Monoclonal antibodies targeting CD39 have been developed and were demonstrated to significantly reduce tumor growth in preclinical cancer models, including as single agent[64]. Furthermore, targeting CD39 in combination with other anticancer strategies, including immunotherapies, and chemotherapy is another promising combination. It was shown recently that anti-CD39 turns “cold” anti-PD1 resistant tumors “hot” and sensitive [192], so the combination therapy of CD39 and PD-1 is expected. However, not all extracellular ADO was inhibited by anti-CD39, and other adenosine production pathways may also be involved in this process. Actually, AMP can be also obtained through the transformation of NAD+ by CD38 and CD203a[9-12]. So combination therapy targeting multiple adenosine-generating enzymes may be more effective. Furthermore, CD39 has vast therapeutic potential in a wide variety of disorders. However, considering the extensive physiological effects of eATP and ADO and the opposite effect of CD39 in some diseases, therapy targeting CD39 requires more in-depth research and individualized treatment.