A Skewed Distribution And Increased Pd-1+V Beta+Cd4+/Cd8+T Cells In Patients With Acute Myeloid Leukemia

JOURNAL OF LEUKOCYTE BIOLOGY(2019)

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摘要
The limited application of immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global T cell immune dysfunction in AML. In this study, we analyzed the distribution characteristics of 24 TCR V beta subfamilies in CD3+, CD4+, and CD8+ T cells in AML patients and healthy controls. The percentage of TCR V beta subfamily T cells was predominately lower in most AML cases, while it was increased in some cases. TCR V beta 2+T cells were increased in AML, particularly TCR V beta 2+CD4+T cells, which were significantly higher. To further address the immunosuppression in different V beta subfamilies, we characterized the distribution of program death-1 (PD-1)+T cells in TCR V beta subfamilies of CD4+ and CD8+T cells. Significantly higher levels of PD-1+V beta+T cells were found for most V beta subfamilies in most AML cases. A higher percentage of PD-1+V beta 2+T cells with a high number of V beta 2+T cells was found in all of the CD3+, CD4+, and CD8+ T cell subsets. Moreover, increasing PD-1+V beta 7.2, V beta 8+, V beta 14+, V beta 16+, and V beta 22+CD8+T cells were distributed in the AML-M5 subtype group compared with the AML-M3 group. In addition, higher PD-1+ V beta 5.2+ and PD-1+ V beta 12+CD8+T cells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD-1+V beta+T cells is a common characteristic of AML, higher PD-1+V beta 2+T cells may be associated with a low antileukemia effect, and higher PD-1+V beta 5.2+ and PD-1+V beta 12+CD8+T cells may be related to poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.
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关键词
TCR, immunosuppression, immune checkpoint
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