Fig. 1

ATP-ADO pathway. The ATP-ADO pathway is critical in regulating immune responses in the tumor microenvironment. Two primary pathways are involved in generating adenosine (ADO): the CD39/CD73 pathway and the CD38/CD203a/CD73 pathway. In the CD39/CD73 pathway, CD39 degrades ATP into ADP and AMP, which is further degraded into ADO by CD73. In the alternative CD38/CD203a/CD73 pathway, nicotinamide adenine dinucleotide (NAD+) is sequentially degraded into ADPR, AMP, and ADO. Adenosine binds to adenosine receptors (i.e., A2AR and A2BR) and inhibits immune cell activation. Additionally, adenosine aminohydrolase (ADA) can convert ADO into inosine. Furthermore, the CD39/CD73 pathway is the predominant mechanism for ADO generation in the TME, and targeting CD39 has emerged as a promising strategy for cancer therapy