Gao Huan, Zhang Tingting, Li Ke, Li Xia
Marine College, Shandong University, Weihai, China.
Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing, China.
Front Immunol. 2025 Mar 6;16:1486868. doi: 10.3389/fimmu.2025.1486868. eCollection 2025.
Recent studies on the pathogenesis of leukemia have led to remarkable advances in disease treatment. Numerous studies have shown the potential and viability of immune responses against leukemia. In the classical pathway, this process is often initiated by the upstream activity of CD39, which hydrolyzes extracellular adenosine triphosphate (ATP) and adenosine diphosphate (ADP) to AMP. Subsequently, CD73 acts on AMP to generate adenosine, contributing to an immunosuppressive microenvironment. However, CD73 can also utilize substrates derived from other molecules through the non-canonical NAD pathway, specifically via the CD38/CD203a/CD73 axis, further enhancing adenosine production and facilitating immune escape. Targeting CD73 has shown potential in disrupting these immunosuppressive pathways, thereby enhancing anti-leukemic immune responses and improving patient outcomes. Inhibiting CD73 not only reduces the levels of immunosuppressive adenosine but also increases the efficacy of existing immunotherapies, such as PD-1/PD-L1 inhibitors, making it a versatile therapeutic target in leukemia treatment. This review discusses the potential of CD73 as a therapeutic target and emphasizes its unique position in the immune escape mechanism of leukemia. Moreover, this review provides an overview of the current research progress and future trends, emphasizing the clinical significance of targeting CD73 and other potential therapeutic strategies in leukemia.
近期关于白血病发病机制的研究已在疾病治疗方面取得了显著进展。大量研究表明了针对白血病的免疫反应的潜力和可行性。在经典途径中，这一过程通常由CD39的上游活性启动，CD39将细胞外三磷酸腺苷（ATP）和二磷酸腺苷（ADP）水解为单磷酸腺苷（AMP）。随后，CD73作用于AMP生成腺苷，促成免疫抑制微环境。然而，CD73还可通过非经典NAD途径利用源自其他分子的底物，具体是通过CD38/CD203a/CD73轴，进一步增强腺苷生成并促进免疫逃逸。靶向CD73已显示出破坏这些免疫抑制途径的潜力，从而增强抗白血病免疫反应并改善患者预后。抑制CD73不仅可降低免疫抑制性腺苷水平，还能提高现有免疫疗法（如PD-1/PD-L1抑制剂）的疗效，使其成为白血病治疗中的一个通用治疗靶点。本综述讨论了CD73作为治疗靶点的潜力，并强调了其在白血病免疫逃逸机制中的独特地位。此外，本综述概述了当前的研究进展和未来趋势，强调了靶向CD73的临床意义以及白血病中的其他潜在治疗策略。
