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.