apyrase and Kidney-Neoplasms

ATP and its ultimate degradation product adenosine are potent extracellular signalling molecules that elicit a variety of pathophysiological functions in the kidney through the activation of P2 and P1 purinergic receptors, respectively. Extracellular purines can modulate immune responses, balancing inflammatory processes and immunosuppression; indeed, alterations in extracellular nucleotide and adenosine signalling determine outcomes of inflammation and healing processes. The functional activities of ectonucleotidases such as CD39 and CD73, which hydrolyse pro-inflammatory ATP to generate immunosuppressive adenosine, are therefore pivotal in acute inflammation. Protracted inflammation may result in aberrant adenosinergic signalling, which serves to sustain inflammasome activation and worsen fibrotic reactions. Alterations in the expression of ectonucleotidases on various immune cells, such as regulatory T cells and macrophages, as well as components of the renal vasculature, control purinergic receptor-mediated effects on target tissues within the kidney. The role of CD39 as a rheostat that can have an impact on purinergic signalling in both acute and chronic inflammation is increasingly supported by the literature, as detailed in this Review. Better understanding of these purinergic processes and development of novel drugs targeting these pathways could lead to effective therapies for the management of acute and chronic kidney disease.

Topics: 5'-Nucleotidase; Acute Kidney Injury; Adenosine; Adenosine Triphosphate; Animals; Antigens, CD; Apyrase; Carcinoma, Renal Cell; Diabetic Nephropathies; Graft Rejection; Humans; Immune Tolerance; Inflammation; Kidney Diseases; Kidney Neoplasms; Kidney Transplantation; Macrophages; Polycystic Kidney Diseases; Receptors, Purinergic P1; Receptors, Purinergic P2; Renal Insufficiency, Chronic; Reperfusion Injury; Signal Transduction; T-Lymphocytes, Regulatory

Natural killer (NK) cell protection from tumor metastases is a critical feature of the host immune response to cancer, but various immunosuppression mechanisms limit NK cell effector function. The ectoenzyme, CD39, expressed on tumor-infiltrating myeloid cells, granulocytes, and lymphocytes, including NK cells, converts extracellular ATP (eATP) into AMP and, thus, potentially suppresses eATP-mediated proinflammatory responses. A CD39-targeting monoclonal antibody (mAb) that inhibits the mouse ectoenzyme CD39 suppressed experimental and spontaneous metastases in a number of different tumor models and displayed superior antimetastatic activity compared with the CD39 inhibitor POM1 and inhibitors and mAbs that block other members of the adenosinergic family (e.g., A2AR and CD73). The antimetastatic activity of anti-CD39 was NK cell and IFNγ dependent, and anti-CD39 enhanced the percentage and quantity of IFNγ produced and CD107a expression in lung-infiltrating NK cells following tumor challenge and anti-CD39 therapy. Using conditional

Topics: Animals; Antibodies, Monoclonal; Antigens, CD; Apyrase; Immune Tolerance; Inflammasomes; Kidney Neoplasms; Killer Cells, Natural; Lung Neoplasms; Melanoma, Experimental; Mice; Mice, Inbred BALB C; Mice, Inbred C57BL; Mice, Knockout; Myeloid Cells; Tumor Cells, Cultured

Tumor microenvironment is important in the progression of clear cell renal cell carcinoma (ccRCC), and its prognostic value is still unclear. Recent reports demonstrated tumor-infiltrating CD39. We immunohistochemically evaluated clinical value of CD39. We found that accumulation of CD39. High CD39

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Antineoplastic Combined Chemotherapy Protocols; Apyrase; Biomarkers, Tumor; Carcinoma, Renal Cell; CD8-Positive T-Lymphocytes; Female; Follow-Up Studies; Humans; Immune Evasion; Kidney Neoplasms; Lymphocytes, Tumor-Infiltrating; Male; Middle Aged; Prognosis; Retrospective Studies; Survival Rate; Tumor Microenvironment; Young Adult