The hypoxic environment of melanoma results in CD73 upregulation on the surface of various tumor microenvironment (TME) cells including tumor cells, stromal cells and infiltrated immune cells. Consequently, CD73 through both enzymatic and none enzymatic functions affect melanoma progression. Overaccumulation of CD73-derived adenosine through interaction with its four G coupled receptors (A₁AR, A_2AAR, A_2BAR, and A₃AR) mediate tumor growth, immune suppression, angiogenesis, and metastasis. This paper aims to comprehensively review the therapeutic potential of CD73 ectonucleotidase targeting in melanoma. To reach this goal, firstly, we summarize the structure, function, regulation, and clinical outcome of CD73 ectonucleotidase. Then, we depict the metabolism and signaling of CD73-derived adenosine along with its progressive role in development of melanoma. Furthermore, the therapeutic potentials of CD73 -adenosine axis targeting is assessed in both preclinical and clinical studies. Targeting CD73-derived adenosine via small molecule inhibitor or monoclonal antibodies studies especially in combination with immune checkpoint blockers including PD-1 and CTLA-4 have shown desirable results for management of melanoma in preclinical studies and several clinical trials have recently been started to evaluate the therapeutic potential of CD73-derived adenosine targeting in solid tumors. Indeed, targeting of CD73-derived adenosine signaling could be considered as a new therapeutic target in melanoma.

黑色素瘤的低氧环境导致CD73在包括肿瘤细胞，基质细胞和浸润的免疫细胞在内的各种肿瘤微环境（TME）细胞表面上表达上调。因此，CD73通过酶促功能和无酶促功能影响黑素瘤的进展。CD73衍生的腺苷通过与其四个G偶联受体（A ₁ AR，A _2A AR，A _2B AR和A ₃AR）介导肿瘤生长，免疫抑制，血管生成和转移。本文旨在全面综述靶向CD73胞外核苷酸酶在黑色素瘤中的治疗潜力。为了达到这个目标，首先，我们总结了CD73胞外核苷酸酶的结构，功能，调控和临床结果。然后，我们描绘了CD73衍生的腺苷的代谢和信号传导及其在黑色素瘤发展中的进行性作用。此外，在临床前和临床研究中都评估了CD73-腺苷轴靶向治疗的潜力。通过小分子抑制剂或单克隆抗体靶向CD73衍生的腺苷的研究，特别是与包括PD-1和CTLA-4的免疫检查点阻断剂的结合，已在临床前研究中显示出可喜的结果，可用于治疗黑色素瘤，最近已开始进行一些临床试验来评估CD73衍生的腺苷靶向治疗实体瘤的治疗潜力。实际上，靶向CD73衍生的腺苷信号传导可以被认为是黑色素瘤的新治疗靶标。