Unleashing the potential of CD39-targeted cancer therapy: Breaking new ground and future prospects
Qiongyan Zhou, Shengwen Shao, Theia Minev, Wenxue Ma
Abstract
The review article titled CD39 Transforming Cancer Therapy by Modulating Tumor Microenvironment published in June 2024 in Cancer Letters provides a comprehensive overview of CD39's multifaceted roles in cancer, particularly its influence on immunoregulation, angiogenesis, and metabolic reprogramming within the tumor microenvironment (TME). This commentary builds on that foundation by incorporating recent advancements in CD39 research, highlighting unresolved issues, and proposing future research directions. We delve into the therapeutic potential of targeting CD39, addressing clinical translation challenges, and exploring the integration of CD39-based strategies into precision oncology. This graphical abstract illustrates the simplified role of CD39 in modulating the immune response within the tumor microenvironment (TME). CD39, an ectonucleotidase expressed on the cell membrane, converts extracellular ATP to ADP and subsequently to adenosine. Adenosine, the final product of this hydrolysis, exerts several immunosuppressive effects: it suppresses the activity of effector T cells, enhances the function of regulatory T cells, inhibits the cytotoxic activity of NK cells, and promotes the expansion and suppressive function of MDSCs. These interactions contribute to an immunosuppressive TME, supporting tumor growth and progression. The figure also highlights potential therapeutic targets to disrupt this pathway. • CD39 modulates immune responses, angiogenesis, and metabolism in the tumor microenvironment. • Emerging CD39-targeted therapies show promise but need furtehr validation and research. • Further studies should focus on personerlized approaches, resistance, and validating CD39 biomarkers.