Onses, immunotherapeutic tactics bring a promising approach in the battle against this devastating neoplasm.4 six In fact, preliminary immunotherapeutic trials have demonstrated enhanced disease-free survival and all round survival in glioblastoma individuals.7 9 Having said that, malignant gliomas are associated with numerous immunomodulatory properties, including absentAReceived October eight, 2012; accepted March 29, 2013. Corresponding Authors: Xin-Gang Li, MD, PhD, Department of Neurosurgery, Qilu Hospital of Shandong University, 107 West Wenhua Rd., Jinan, China 250012 ([email protected]); Xun Qu, PhD, Institute of Simple Healthcare Sciences and Crucial Laboratory of Cardiovascular Proteomics of Shandong Province, Qilu Hospital of Shandong University, 107 West Wenhua Rd., Jinan, China 250012 (quxun@sdu. edu.cn).# The Author(s) 2013. Published by Oxford University Press on behalf on the Society for Neuro-Oncology. All rights reserved. For permissions, please e-mail: [email protected] et al.: The synergic effect among glioma cells and infiltrating T cells enhances local immunosuppressiontumor-specific antigen expression, immune checkpoint overexpression, immunosuppressive cytokine secretion, effector lymphocyte anergy, recruitment and induction of regulatory T cells (Tregs) and M2 macrophages, and immune inhibitory issue accumulation.ten,11 As a result, antitumor immunity is suppressed profoundly and manipulated to market tumor progression. Adenosine has been identified as a universal and potent immune suppressor.12 The surface-expressing ectoenzymes, CD39/ectonucleoside triphosphate diphosphohydrolase (ENTPD1) and CD73/ecto-5 -nucleotidase (NT5E), sequentially convert pro-inflammatory ATP, released from stressed or damaged cells into extracellular space, into AMP and adenosine, respectively. Adenosine deaminase (ADA) would be the adverse regulator accountable for the rapid deactivation of anti-inflammatory adenosine. Hence, the adenosine balance maintained by the ectoenzymes CD39-CD73-ADA is pivotal for immune homeostasis.13 Having said that, excess adenosine accumulation is related with specific pathological situations, including chronic inflammations and tumors, which activates Gs-protein-coupled adenosine A2aR receptors expressed by many different immune cells and elevates the intracellular cAMP level.Arginase, Microorganism Epigenetic Reader Domain Consequently, potent immunosuppression is induced, causing abrogated T-cell proliferation, Th1/ Th2 shifting, Treg induction, and inhibition of macrophage activation.2-Hydroxybutyric acid custom synthesis 14 16 To date, the CD39-CD73adenosine pathway has been recognized as a crucial immunosuppressive mechanism having a promising therapeutic prospect in oncology.PMID:24732841 17 Nevertheless, various particulars haven’t however been characterized. For example, although the value of tumor-derived CD73 in tumorigenesis, metastasis, and immunosuppression has been demonstrated each in vitro and in vivo,18 20 the CD39 activity in gliomas has not been confirmed.21,22 On the other hand, in spite of the coexpression of CD73 and CD39 in murine CD4+CD25+Foxp3+ Tregs,23 the expression and activity of CD73 in human CD4+CD39+ T lymphocytes are practically absent.24 26 Within this study, the phenotypic and functional qualities of the ectoenzymes expressed by glioma cells and glioma-infiltrating CD4+ T lymphocytes had been evaluated in detail. Depending on the distinct but complementary ectoenzyme status of these 2 cell populations, we demonstrate that CD73+ glioma cells contribute to nearby adenosinergic immunosuppression synergistically with infiltrating CD.
