en O24: Functional Role of the K2P Potassium Channel TASK-3 in Glioma تحقیقات پایه در علوم اعصاب Basic research in Neuroscience پژوهشي Research --- Open Access, CC-BY-NC <div style="text-align: center;"><span style="text-align: center; color: rgb(0, 0, 0); text-transform: none; text-indent: 0px; letter-spacing: normal; font-family: Tahoma; font-size: 12px; font-style: normal; font-weight: 400; word-spacing: 0px; float: none; display: inline !important; white-space: normal; orphans: 2; widows: 2; background-color: rgb(251, 250, 249); font-variant-ligatures: normal; font-variant-caps: normal; -webkit-text-stroke-width: 0px; text-decoration-style: initial; text-decoration-color: initial;">لطفاً به چکیده انگلیسی مراجعه شود.</span></div> <div style="text-align: justify;">TASK-3, a two-pore-domain (K2P) potassium channel, has been implicated as important regulator for the effector function and proliferation of T-cells. Interestingly, TASK-3 has also a functional impact on tumor cells. Therefore, we sought to investigate whether TASK3 modulation might have a therapeutic potential for malignant gliomas by a variety of phenotypical and functional in vitro assays mimicking tumor microenvironment such as hypoxia and an in vivo mouse model for malignant glioma. GL261 glioma cells demonstrated higher proliferation rates under hypoxia, while proliferation and viability of WT (wildtype) T-cells was significantly reduced. Of note, TASK3-/- T-cells were more resistant to hypoxia-induced anergy and cell death indicating a potential advantage in immune-mediated tumor defense. In accordance, TASK-3-/- mice demonstrated a longer symptom-free survival in the GL261 malignant glioma model compared to WT mice (31 versus 23 days). To dissect an immune-cell mediated effect, we performed an adoptive transfer of splenocytes in RAG-/- mice, which do not contain mature B- or T-cells. Transferring TASK-3-/- splenocytes, we observed prolonged symptom-free survival (21 days) compared to WT splenocytes (17 days). Therefore, our results indicate a role of TASK3 in immune-cell mediated tumor defense mechanisms providing first evidence for a new therapeutic target in glioma therapy.</div> <div style="text-align: justify;"></div> Potassium Channel, Glioma, Tumor 24 24 http://shefayekhatam.ir/browse.php?a_code=A-10-24-1096&slc_lang=en&sid=1 Thomas Müntefering Thomas Müntefering Thomas.Muentefering@ukmuenster.de 100319475328460015416 100319475328460015416 Yes Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany Tobias Ruck Tobias Ruck 100319475328460015417 100319475328460015417 No Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany Christian Thomas Christian Thomas 100319475328460015418 100319475328460015418 No Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany Ole Simon Ole Simon 100319475328460015419 100319475328460015419 No Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany Petra Hundehege Petra Hundehege 100319475328460015420 100319475328460015420 No Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany Oliver Grauer Oliver Grauer 100319475328460015421 100319475328460015421 No Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany Sven Meuth Sven Meuth 100319475328460015422 100319475328460015422 No Institute of Translational Neurology, University of Münster, Münster, Germany Institute of Translational Neurology, University of Münster, Münster, Germany