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• W2433304613 abstract "// Patricia A. Toniolo 1, 2 , Suhu Liu 1 , Jennifer E. Yeh 1 , Darwin Q. Ye 1 , José Alexandre M. Barbuto 2 , David A. Frank 1 1 Department of Medical Oncology, Dana-Farber Cancer Institute, and Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA, USA 2 Department of Immunology, Institute of Biomedical Sciences, University of Sao Paulo, Sao Paulo, Brazil Correspondence to: David A. Frank, email: david_frank@dfci.harvard.edu Keywords: monocytes, dendritic cells, SOCS5, CLL, STAT3 Received: December 01, 2015     Accepted: May 28, 2016     Published: June 15, 2016 ABSTRACT One cause of morbidity and mortality in chronic lymphocytic leukemia (CLL) is infection, which results from defects in a number of components of the immune system. In particular, dendritic cells (DCs) are functionally defective in patients with CLL. To understand the molecular mechanism for this abnormality, we focused on signal transduction pathways that regulate the function of monocyte-derived dendritic cells (Mo-DCs). Monocytes from CLL patients exhibit high IL-4Rα expression due to the enhanced activation of STAT3. However, IL-4R signaling is decoupled from activation of its downstream mediator STAT6 by enhanced levels of the negative regulator SOCS5. This impairs differentiation of functionally mature DCs leading to decreased expression of HLA-DR and costimulatory molecules, and reduced secretion of pro-inflammatory cytokines in LPS-activated DCs. Moreover, Mo-DCs from CLL patients display a decreased ability to induce pro-inflammatory T-cell responses. IL-10-treatment of monocytes from healthy donors mimics the alteration in signaling observed in CLL patients, through enhanced STAT3-dependent expression of SOCS5. The higher level of SOCS5 inhibits STAT6 activation and leads to defective DC differentiation. These findings indicate that SOCS5 mediates the impaired function of DCs in CLL patients, and has the potential to be a new therapeutic target for reversing cancer-associated immune suppression." @default.
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• W2433304613 date "2016-06-15" @default.
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• W2433304613 title "Deregulation of SOCS5 suppresses dendritic cell function in chronic lymphocytic leukemia" @default.
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• W2433304613 doi "https://doi.org/10.18632/oncotarget.10093" @default.
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