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• W2895893228 endingPage "1496" @default.
• W2895893228 startingPage "1488" @default.
• W2895893228 abstract "Interleukin 35 (IL-35) is a potent immunosuppressive cytokine, consisting of an Epstein-Barr virus-induced gene 3 (EBI3) subunit and a p35 subunit. IL-35 is mainly produced by regulatory T and regulatory B cells, and plays a crucial role in the development and prevention of infectious and autoimmune diseases. However, the effect of IL-35 in malignant disease is not well understood. In this study, we demonstrated that breast cancer cells (BCCs) also expressed and secreted IL-35 and higher level of IL-35 in BCCs was closely associated with poor prognosis of patients and was an independent unfavorable prognostic factor for breast cancer. Subsequent study revealed that BCC-derived IL-35 inhibited conventional T (Tconv) cell proliferation and further induced suppressed Tconv cells into IL-35-producing induced regulatory T (iTr35) cells. Furthermore, BCC-derived IL-35 promoted the secretion of inhibitory cytokine IL-10 and obviously decreased the secretion of Th1-type cytokine IFN-γ and Th17-type cytokine IL-17 in Tconv cells. Meanwhile, the expression of inhibitory receptor CD73 was also elevated on the surface of Tconv cells following the BCCs' supernatant treatment. Mechanistically, BCC-derived IL-35 exhausted Tconv cells and induced iTr35 by activating transcription factor STAT1/STAT3. Hence, our results indicate functions of BCC-derived IL-35 in promoting tumor progression through proliferation inhibition of tumor-infiltrating Tconv cells and induction of iTr35 cells in tumor microenvironment. This study highlights that IL-35 produced by BCCs are a potential therapeutic target for breast cancer." @default.
• W2895893228 created "2018-10-26" @default.
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• W2895893228 date "2018-10-13" @default.
• W2895893228 modified "2023-10-15" @default.
• W2895893228 title "Breast cancer cell–derived IL-35 promotes tumor progression via induction of IL-35-producing induced regulatory T cells" @default.
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• W2895893228 doi "https://doi.org/10.1093/carcin/bgy136" @default.
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• W2895893228 hasPublicationYear "2018" @default.
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