Cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints.

Extracellular adenosine has recently been identified as an immunological checkpoint mediator that hinders the immune response to malignancies. The production of adenosine is facilitated by the enzymatic activity of CD39 and CD73. There is an increasing body of evidence suggesting that CD39 and CD73, which are considered to be emerging immunological checkpoints, can transform adenosine triphosphate (ATP)-mediated pro-inflammatory tumor microenvironment (TME) into an adenosine-mediated immunosuppressive through purinergic pathway. The aim of this study was to review macrophages-based cancer immunotherapy by adenosinergic CD39 and CD73 as emerging immune checkpoints. We searched the PubMed, EMBASE, Web of Science, and Medline (Ovid) databases to find relevant studies between December 30, 2010, and December 30, 2024. The search strategy encompassed utilization of Cancer, Immune checkpoints, CD39, CD73, Immunotherapy as keywords. The case reports, reviews, evaluations, originals, and earlier meta-analyses were all included in the study. The inclusion criteria were the researches that investigated the functions of the adenosinergic immunological checkpoints CD39 and CD73 in cancer immunotherapy. Clinical studies have examined small molecule inhibitors or monoclonal antibodies that target the CD39/CD73 pathway in recent years. Cancer immunotherapy might profit from therapeutic inhibition of CD39 and CD73’s enzymatic activity, given that these two proteins are crucial for the conversion of ATP into adenosine. Multiple types of monoclonal antibodies have been developed and shown to inhibit CD39 or CD73. One benefit of using monoclonal antibodies to block CD39 and CD73 is that antibody medications usually have lengthy serum half-lives. Inhibiting CD39 and CD73 may contribute to limiting the progression of tumors and boost anti-tumor responses. Currently, one of the most promising strategies in immuno-oncology is to target CD39 and CD73 due to their extensive immune regulatory effects on tumor immunity.