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A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ T cells in patients with acute myeloid leukemia
Jingying Huang1, Jiaxiong Tan1,2, Youchun Chen1
1Institute of Hematology, School of Medicine, Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, China.
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 Vβ subfamilies in CD3+, CD4+, and CD8+ T cells in AML patients and healthy controls. The percentage of TCR Vβ subfamily T cells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+T cells were increased in AML, particularly TCR Vβ2+CD4+T cells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death-1 (PD-1)+T cells in TCR Vβ subfamilies of CD4+ and CD8+T cells. Significantly higher levels of PD-1+Vβ+T cells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD-1+Vβ2+T cells with a high number of Vβ2+T cells was found in all of the CD3+, CD4+, and CD8+ T cell subsets. Moreover, increasing PD-1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+T cells were distributed in the AML-M5 subtype group compared with the AML-M3 group. In addition, higher PD-1+ Vβ5.2+ and PD-1+ Vβ12+CD8+T cells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD-1+Vβ+T cells is a common characteristic of AML, higher PD-1+Vβ2+T cells may be associated with a low antileukemia effect, and higher PD-1+Vβ5.2+ and PD-1+Vβ12+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.
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 Vβ subfamilies in CD3+, CD4+, and CD8+ T cells in AML patients and healthy controls. The percentage of TCR Vβ subfamily T cells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+T cells were increased in AML, particularly TCR Vβ2+CD4+T cells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death-1 (PD-1)+T cells in TCR Vβ subfamilies of CD4+ and CD8+T cells. Significantly higher levels of PD-1+Vβ+T cells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD-1+Vβ2+T cells with a high number of Vβ2+T cells was found in all of the CD3+, CD4+, and CD8+ T cell subsets. Moreover, increasing PD-1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+T cells were distributed in the AML-M5 subtype group compared with the AML-M3 group. In addition, higher PD-1+ Vβ5.2+ and PD-1+ Vβ12+CD8+T cells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD-1+Vβ+T cells is a common characteristic of AML, higher PD-1+Vβ2+T cells may be associated with a low antileukemia effect, and higher PD-1+Vβ5.2+ and PD-1+Vβ12+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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