التفاصيل البيبلوغرافية
| العنوان: |
TGF-β upregulates CD70 expression and induces exhaustion of effector memory T cells in B-cell non-Hodgkin's lymphoma. |
| المؤلفون: |
Yang, Z-Z, Grote, D M, Xiu, B, Ziesmer, S C, Price-Troska, T L, Hodge, L S, Yates, D M, Novak, A J, Ansell, S M |
| المصدر: |
Leukemia (08876924); Sep2014, Vol. 28 Issue 9, p1872-1884, 13p, 8 Graphs |
| مصطلحات موضوعية: |
TRANSFORMING growth factors-beta, T cells, IMMUNOSUPPRESSION, HODGKIN'S disease, APOPTOSIS |
| مستخلص: |
Transforming growth factor beta (TGF-β) has an important role in mediating T-cell suppression in B-cell non-Hodgkin lymphoma (NHL). However, the underlying mechanism responsible for TGF-β-mediated inhibition of effector memory T (Tm) cells is largely unknown. As reported here, we show that exhaustion is a major mechanism by which TGF-β inhibits Tm cells, and TGF-β mediated exhaustion is associated with upregulation of CD70. We found that TGF-β upregulates CD70 expression on effector Tm cells while it preferentially induces Foxp3 expression in naive T cells. CD70 induction by TGF-β is Smad3-dependent and involves IL-2/Stat5 signaling. CD70+ T cells account for TGF-β-induced exhaustion of effector Tm cells. Both TGF-β-induced and preexisting intratumoral CD70+ effector Tm cells from B-cell NHL have an exhausted phenotype and express higher levels of PD-1 and TIM-3 compared with CD70− T cells. Signaling transduction, proliferation and cytokine production are profoundly decreased in these cells, and they are highly susceptible to apoptosis. Clinically, intratumoral CD70-expressing T cells are prevalent in follicular B-cell lymphoma (FL) biopsy specimens, and increased numbers of intratumoral CD70+ T cells correlate with an inferior patient outcome. These findings confirm TGF-β-mediated effector Tm cell exhaustion as an important mechanism of immune suppression in B-cell NHL. [ABSTRACT FROM AUTHOR] |
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| قاعدة البيانات: |
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