A skewed distribution and increased PD-1+Vβ+CD4+/CD8+T cells in patients with acute myeloid leukemia
A skewed distribution and increased PD-1+Vβ+CD4+/CD8+T cells in patients with acute myeloid leukemia
复制标题
急性髓系白血病患者中 PD-1 Vβ CD4 /CD8 T 细胞的分布偏斜和增加
DOI：
10.1002/jlb.ma0119-021r
复制
发表时间：
2019-09-01
影响因子：
5.5
通讯作者：
Li, Yangqiu
中科院分区：
文献类型：
--
作者：
Huang, Jingying;Tan, Jiaxiong;Li, Yangqiu
免疫治疗在急性髓系白血病（AML）中的应用有限，可能是由于对AML中的整体T细胞免疫功能障碍缺乏了解。在这项研究中，我们分析了24个TCR V β亚家族在AML患者和健康对照者的CD 3+、CD 4+和CD 8 + T细胞中的分布特征。在大多数AML病例中，TCR V β亚家族T细胞的百分比主要较低，而在某些病例中则有所增加。AML中TCR V β 2+T细胞增加，特别是TCR V β 2+ CD 4 +T细胞，其显著更高。为了进一步解决不同V β亚家族中的免疫抑制，我们表征了程序性死亡-1（PD-1）+T细胞在CD 4+和CD 8 +T细胞的TCR V β亚家族中的分布。在大多数AML病例中，发现大多数V β亚家族的PD-1+V β +T细胞水平显著较高。在所有CD 3+、CD 4+和CD 8 + T细胞亚群中发现PD-1+V β 2 + T细胞百分比较高，V β 2+ T细胞数量较多。此外，与AML-M3组相比，AML-M5亚型组中PD-1+V β 7.2、V β 8+、V β 14+、V β 16+和V β 22+ CD 8 +T细胞的分布增加。此外，较高的PD-1+ V β 5.2+和PD-1+ V β 12+ CD 8 +T细胞与对化疗反应较差的AML患者相关。总之，PD-1+V β +T细胞增加是AML的共同特征，较高的PD-1+V β 2+T细胞可能与低抗白血病效应相关，较高的PD-1+V β 5.2+和PD-1+V β 12+ CD 8 +T细胞可能与AML的不良预后相关。这些特征可能值得考虑作为AML临床结局的免疫生物标志物。
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.