A skewed distribution and increased PD-1+Vβ+CD4+/CD8+ Tcells in patients with acute myeloid leukemia.

Abstract

The limited application of immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global Tcell immune dysfunction in AML. In this study, we analyzed the distribution characteristics of 24 TCR Vβ subfamilies in CD3+, CD4+, and CD8+ Tcells in AML patients and healthy controls. The percentage of TCR Vβ subfamily Tcells was predominately lower in most AML cases, while it was increased in some cases. TCR Vβ2+Tcells were increased in AML, particularly TCR Vβ2+CD4+Tcells, which were significantly higher. To further address the immunosuppression in different Vβ subfamilies, we characterized the distribution of program death-1 (PD-1)+Tcells in TCR Vβ subfamilies of CD4+ and CD8+Tcells. Significantly higher levels of PD-1+Vβ+Tcells were found for most Vβ subfamilies in most AML cases. A higher percentage of PD-1+Vβ2+Tcells with a high number of Vβ2+Tcells was found in all of the CD3+, CD4+, and CD8+ Tcell subsets. Moreover, increasing PD-1+Vβ7.2, Vβ8+, Vβ14+, Vβ16+, and Vβ22+CD8+Tcells 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+Tcells were associated with AML patients who had a poor response to chemotherapy. In conclusion, increased PD-1+Vβ+Tcells is a common characteristic of AML, higher PD-1+Vβ2+Tcells may be associated with a low antileukemia effect, and higher PD-1+Vβ5.2+ and PD-1+Vβ12+CD8+Tcells may be related to poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.