CHARACTERISTIC OF PD-1+VΒ+CD4+ AND PD-1+VΒ+CD8+ T CELLS IN PATIENTS WITH ACUTE MYELOID LEUKEMIA

Abstract

T cell dysfunction is associated with disease relapse and progress in leukemia. Restoring anti-cancer T cell function could be carried out by immune checkpoint blockade. However, the limited application of such immunotherapy in acute myeloid leukemia (AML) may be due to poor understanding of the global T cell dysfunction. In this study, we analyzed the distribution of 24 TCR Vβ subfamilies in CD3+, CD4+, and CD8+ T cells in peripheral blood from 10 de novo AML patients and 18 healthy individuals (HI). We firstly established the global distribution pattern of Vβ repertoire in HI and found a different distribution pattern for Vβ repertoire in AML. The number of Vβ+T cells was predominately lower in most AML cases, while increased in some cases. Vβ2+T cells were increased in AML, particularly 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 Vβ + CD4+ and CD8+T cells. Significantly higher levels of PD-1+Vβ+T cells were found in the majority of the AML cases. In CD3+ T cells, higher PD-1+ Vβ+ T cells were found in 22 out of the 24 Vβ subfamilies with the exception of Vβ11 and Vβ14. Similarly, higher PD-1+ Vβ+ T cells were found in 23 out of the 24 Vβ subfamilies in CD4+ T cells and in 11 Vβ subfamily CD8+ T cells. 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. 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 are a common characteristic of AML, which may be associated with a low anti-leukemia effect and poor prognosis in AML. These characteristics may be worth considering as immune biomarkers for clinical outcome in AML.