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- W201017839 abstract "Chronic lymphocytic leukemia (CLL) is characterized by the accumulation of CD5 + CD19 + B cells in the peripheral blood, and in primary and secondary lymphoid organs. A major complication associated with CLL is severe recurrent infections, which are often fatal. Vulnerability to infection is due to a wide variety of immunological defects, yet the initiating events of immunodeficiency in CLL are unclear. Using CLL patient samples and a mouse model of CLL, we have discovered that plasmacytoid dendritic cells (pDCs), which function underpins the activity of effector immune cells critical for anti-viral immunity and anti-tumor responses, are reduced in number and functionally impaired in progressive CLL. As a result, the levels of interferon alpha (IFNa) production, a cytokine critical for immunity, are markedly reduced. Lower pDC numbers with impaired IFNa production was due to the decreased expression of FMS-like tyrosine kinase 3 receptor (Flt3) and Toll-like receptor 9 (TLR9), respectively. Reduced Flt3 expression was reversed using inhibitors of TGF-b and TNF, an effect correlating with a reduction in tumor load. Defects in pDC numbers and function offer new insight into mechanisms underpinning the profound immunodeficiency affecting CLL patients and provide a potentially novel avenue for restoring immunocompetency in CLL." @default.
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- W201017839 date "2014-11-01" @default.
- W201017839 modified "2023-09-24" @default.
- W201017839 title "S-15" @default.
- W201017839 doi "https://doi.org/10.1016/j.cyto.2014.07.235" @default.
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