apyrase and Carcinoma--Renal-Cell

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

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