کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
8721331 | 1589400 | 2018 | 27 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
CD8+Â T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients
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کلمات کلیدی
موضوعات مرتبط
علوم زیستی و بیوفناوری
ایمنی شناسی و میکروب شناسی
ایمونولوژی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: CD8+Â T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients CD8+Â T cells expressing both PD-1 and TIGIT but not CD226 are dysfunctional in acute myeloid leukemia (AML) patients](/preview/png/8721331.png)
چکیده انگلیسی
Acute myeloid leukemia (AML) is one of the most common types of leukemia among adults with an overall poor prognosis and very limited treatment management. Immune checkpoint blockade of PD-1 alone or combined with other immune checkpoint blockade has gained impressive results in murine AML models by improving anti-leukemia CD8+ T cell function, which has greatly promoted the strategy to utilize combined immune checkpoint inhibitors to treat AML patients. However, the expression profiles of these immune checkpoint receptors, such as co-inhibitory receptors PD-1 and TIGIT and co-stimulatory receptor CD226, in T cells from AML patients have not been clearly defined. Here we have defined subsets of CD8+ and CD4+ T cells in the peripheral blood (PB) from newly diagnosed AML patients and healthy controls (HCs). We have observed increased frequencies of PD-1- and TIGIT- expressing CD8+ T cells but decreased occurrence of CD226-expressing CD8+ T cells in AML patients. Further analysis of these CD8+ T cells revealed a unique CD8+ T cell subset that expressed PD-1 and TIGIT but displayed lower levels of CD226 was associated with failure to achieve remission after induction chemotherapy and FLT3-ITD mutations which predict poor clinical prognosis in AML patients. Importantly, these PD-1+ TIGIT+ CD226â CD8+ T cells are dysfunctional with lower expression of intracellular IFN-γ and TNF-α than their counterparts in HCs. Therefore, our studies revealed that an increased frequency of a unique CD8+ T cell subset, PD-1+ TIGIT+ CD226â CD8+ T cells, is associated with CD8+ T cell dysfunction and poor clinical prognosis of AML patients, which may reveal critical diagnostic or prognostic biomarkers and direct more efficient therapeutic strategies.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Clinical Immunology - Volume 190, May 2018, Pages 64-73
Journal: Clinical Immunology - Volume 190, May 2018, Pages 64-73
نویسندگان
Mengjie Wang, Jin Bu, Maohua Zhou, Jessica Sido, Yu Lin, Guanfang Liu, Qiwen Lin, Xiuzhang Xu, Jianmei W. Leavenworth, Erxia Shen,