IL-6 produced by tumor cells promotes their survival, conferring a poor prognosis in cancer patients. IL-6 also contributes to immunosuppression of CD4+ T cell-mediated antitumor effects. In this study, we focused on the impact of IL-6 trans-signaling mediated by soluble IL-6 receptors (sIL-6R) expressed in tumor-bearing hosts. Higher levels of sIL-6R circulating in blood was observed in tumor-bearing mice, whereas the systemic increase of sIL-6R was not prominent in tumor-bearing mice with myeloid cell-specific conditional deletion of IL-6R even when tumor cells produced sIL-6R. Abundant sIL-6R was released by CD11b+ cells from tumor-bearing mice but not tumor-free mice. Notably, IL-6-mediated defects in Th1 differentiation, T cell helper activity for tumor-specific CD8+ T cells and downstream antitumor effects were rescued by myeloid-specific deletion of sIL-6R. Expression of the T cell transcription factor c-Maf was upregulated in CD4+ T cells primed in tumor-bearing mice in an IL-6-dependent manner. Investigations with c-Maf loss-of-function T cells revealed that c-Maf activity was responsible for IL-6/sIL-6R-induced Th1 suppression and defective T cell-mediated antitumor responses. In cancer patients, myeloid cell-derived sIL-6R was also possibly associated with Th1 suppression and c-Maf expression. Our results argued that increased expression of sIL-6R from myeloid cells and subsequent c-Maf induction were adverse events for counteracting tumor-specific Th1 generation. Overall, this work provides a mechanistic rationale for sIL-6R targeting to improve the efficacy of T cell-mediated cancer immunotherapy.
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Publication date: Available online 4 January 2018 Source: European Journal of Radiology Author(s): Peiyao Zhang, Jing Wang, Qin Xu, Zhen...
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Medicine by Alexandros G. Sfakianakis,Anapafseos 5 Agios Nikolaos 72100 Crete Greece,00302841026182, Butyric Acid from Probiotic Staphyloco...
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Does CBD Oil Lower Blood Pressure? This article was originally published at SundayScaries." Madeline Taylor POSTED ON January 13, 20...
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Medicine by Alexandros G. Sfakianakis,Αλέξανδρος Γ. Σφακιανάκης A Novel Technique for Endoscopic Repair of Large Anterior Skull Base Defect...
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Abstract The development of focused ion beam-scanning electron microscopy (FIB-SEM) techniques has allowed high-resolution 3D imaging of n...
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Vol.48 No.2 from #AlexandrosSfakianakis via Alexandros G.Sfakianakis on Inoreader http://ift.tt/1S2Z7n2 via IFTTT
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