کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
5526568 1547066 2016 16 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Original ResearchThe blockage of Notch signalling promoted the generation of polymorphonuclear myeloid-derived suppressor cells with lower immunosuppression
موضوعات مرتبط
علوم زیستی و بیوفناوری بیوشیمی، ژنتیک و زیست شناسی مولکولی تحقیقات سرطان
پیش نمایش صفحه اول مقاله
Original ResearchThe blockage of Notch signalling promoted the generation of polymorphonuclear myeloid-derived suppressor cells with lower immunosuppression
چکیده انگلیسی


- Notch signalling was inhibited significantly in myeloid-derived suppressor cells (MDSCs) in tumour-bearing mice.
- MDSCs without Notch signalling were down-regulated their immunosuppressive activity.
- The blockage of Notch signalling in MDSCs reduced the impairment on dendritic cell development.
- Notch signalling inhibited the generation of polymorphonuclear-MDSCs but improved the production of mononuclear MDSCs both in vitro and in vivo.
- Stat3 pathway mediated the Notch-signalling effects on MDSCs.

Myeloid-derived suppressor cells (MDSCs) mostly consisting of polymorphonuclear (PMN)-MDSCs and mononuclear MDSCs have been considered to play critical roles in immunosuppression, angiogenesis, invasion and metastases of various tumours. However, it is still unclear the regulated mechanisms underlying the generation and immunosuppression of two major MDSC subsets. Here, we report Notch signalling was inhibited significantly in tumour-bearing mouse MDSCs, in which PMN-MDSCs were the major population. MDSCs without recombination signal binding protein-Jк (RBP-J), the critical transcription factor mediating signalling from all four mammalian Notch receptors, reduced their ability of inhibiting the proliferation and activation of allogenic T cells. RBP-J-deficient MDSCs could not down-regulate the expression of co-stimulation molecules on dendritic cells (DCs). The antigen presentation capacity of DCs co-cultured with RBP-J-deficient MDSCs was not impaired in contrast to controls. Moreover, we show the blockage of Notch signalling could improve the generation of PMN-MDSCs but inhibit the production of mononuclear MDSCs both in vitro and in vivo. Stat3 pathway was suppressed in MDSCs blocked Notch signalling and Stat3 activation by IL-6 could reverse the phenotype and immunosuppression of Notch signalling-deficient MDSCs. Therefore, targeting Notch signalling may be an effective therapeutic strategy in tumour therapy.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: European Journal of Cancer - Volume 68, November 2016, Pages 90-105
نویسندگان
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