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

J Leukoc Biol. 2019 Sep;106(3):725-732. doi: 10.1002/JLB.MA0119-021R. Epub 2019 May 28.

Abstract

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.

Keywords: TCR; immune checkpoint; immunosuppression.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • CD8-Positive T-Lymphocytes / immunology*
  • Female
  • Humans
  • Leukemia, Myeloid, Acute / drug therapy
  • Leukemia, Myeloid, Acute / immunology*
  • Male
  • Middle Aged
  • Programmed Cell Death 1 Receptor / metabolism*
  • Receptors, Antigen, T-Cell, alpha-beta / metabolism*
  • Treatment Outcome
  • Young Adult

Substances

  • Programmed Cell Death 1 Receptor
  • Receptors, Antigen, T-Cell, alpha-beta