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• W2742440809 abstract "// Liangliang Wu 1, * , Zhaoyang Deng 2, * , Yaojun Peng 1 , Lu Han 3 , Jing Liu 1 , Linxiong Wang 1 , Bohua Li 4 , Jian Zhao 4 , Shunchang Jiao 1, 3 and Huafeng Wei 1 1 Key Lab of Cancer Center, General Hospital of Chinese PLA & Beijing Key Laboratory of Cell Engineering & Antibody, Beijing, China 2 Surgical Division, General Hospital of Chinese PLA, Beijing, China 3 Department of Internal Oncology, General Hospital of Chinese PLA, Beijing, China 4 Shanghai Key Laboratory for Molecular Imaging, Shanghai University of Medicine & Health Sciences, Shanghai, China * These authors have contributed equally to the work Correspondence to: Huafeng Wei, email: foxp3_smmu@163.com Shunchang Jiao, email: jiaosc@me.com Keywords: MDSC, ovarian cancer, IL-6, IL-10, STAT3 Received: March 13, 2017    Accepted: June 27, 2017    Published: August 10, 2017 ABSTRACT Myeloid-derived suppressor cells (MDSC) play a key immunosuppressive role in various types of cancer, including ovarian cancer (OC). In this study, we characterized CD14 + HLA-DR −/lo MDSC with a typical monocytic phenotype (M-MDSC) in the peripheral blood (PB) and ascites from OC patients. Compared to healthy donors, OC patients had a significantly increased abundance of M-MDSC in both PB and ascites; importantly, their abundance in both compartments was inversely associated with the prognosis where OC patients with higher level of M-MDSC having a shorter relapse-free survival. Intriguingly, we demonstrated that M-MDSC could be readily induced by ascitic fluids (AF) from OC patients, which was predominantly dependent on IL-6, IL-10 and STAT3 activation as neutralization of IL-6 and/or IL-10 or inhibition of STAT3 abrogated MDSC’s expansion while recombinant IL-6 and IL-10 recapitulated the expansive effect of AF; furthermore, predominantly elevated levels of IL-6 and IL-10 has been noted in the AF which was positively correlated with the abundance of M-MDSC as well as poor prognosis of OC patients. As expected, we observed that AF-driven STAT3 activation upregulated the expression of arginase (ARG1) and inducible nitric oxide synthase (iNOS) in induced M-MDSC through which these MDSC executed the immunosuppressive activity. Taken together, these results demonstrate that abundant M-MDSC are present in both periphery and ascites of OC patients whose accumulation and suppressive activity is critically attributable to ascites-derived IL-6 and IL-10 and their downstream STAT3 signal, thus providing a potentially novel therapeutic option by locally targeting MDSC to improve antitumor efficacy." @default.
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• W2742440809 date "2017-08-10" @default.
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• W2742440809 title "Ascites-derived IL-6 and IL-10 synergistically expand CD14+HLA-DR-/low myeloid-derived suppressor cells in ovarian cancer patients" @default.
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• W2742440809 doi "https://doi.org/10.18632/oncotarget.20164" @default.
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