{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nNT5E (also known as CD73) encodes an ecto‐5′‐nucleotidase that catalyzes the dephosphorylation of extracellular AMP to adenosine, thereby establishing a critical adenosinergic pathway. This enzymatic activity is pivotal for regulating extracellular adenosine levels, which in turn control immune responses, inflammation, and intercellular communication in both normal and pathological settings."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nWithin the tumor microenvironment, CD73‐generated adenosine contributes to immune evasion by suppressing the activation and proliferation of effector T cells and natural killer (NK) cells. Several studies across distinct malignancies—including triple‐negative breast cancer, ovarian carcinoma, glioblastoma, and others—demonstrate that CD73 activity (whether expressed on cancer cells, infiltrating immune cells, or stromal elements such as specialized regulatory T cells) promotes a local immunosuppressive niche that fosters tumor growth, sustains cancer-initiating cell properties, and impairs anti‐tumor immunotherapy responses."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "4", "end_ref": "11"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nIn addition to modulating immune responses, NT5E/CD73 influences tumor cell behavior by promoting proliferation, migration, invasion, and metastasis. In various cancers such as breast, hepatocellular, prostate, and melanoma, enhanced CD73 expression supports tumor growth and dissemination through adenosine receptor–mediated signaling as well as through non-enzymatic interactions that affect cell adhesion and the extracellular matrix."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "12", "end_ref": "17"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFurthermore, CD73 activity has been implicated in mediating resistance to chemotherapy and targeted agents. In glioblastoma and other malignancies, high CD73 levels promote chemoresistance—by modulating adenosine production that activates downstream survival pathways—while its inhibition can sensitize tumor cells to cytotoxic drugs and improve therapeutic outcomes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "18", "end_ref": "21"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nBeyond its roles in cancer, NT5E regulates several key cellular processes such as cell adhesion and migration in non–tumor contexts. For example, CD73 influences the transmigration of immune cells (including lymphocytes and platelets) across endothelial and epithelial barriers, and is involved in the mechanical regulation of mesenchymal stromal cell migration via interactions with integrins and modulation of the actin cytoskeleton."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "22", "end_ref": "24"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nNT5E/CD73 also exerts broad influences on tissue homeostasis and non–tumor pathology. Its expression in cancer-associated fibroblasts, endothelial cells, and epithelial cells is linked to processes such as angiogenesis, fibrosis, epithelial-to-mesenchymal transition, and even cardiovascular calcification. In addition, by modulating extracellular NAD+ precursor availability and contributing to both enzymatic and non-enzymatic functions, CD73 has been associated with prognostic implications in colorectal cancer, vascular diseases, and metabolic regulation. Collectively, these findings highlight the central role of CD73 in linking extracellular nucleotide metabolism to diverse cellular processes."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "25", "end_ref": "36"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nFinally, emerging clinical evidence indicates that CD73 expression not only drives tumor progression and resistance to therapy but also correlates with diverse prognostic outcomes depending on cancer type. 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