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. 2017 Oct;29(5):463-470.
doi: 10.21147/j.issn.1000-9604.2017.05.11.

Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia

Jiaxiong Tan  1 , Shaohua Chen  1 , Yuhong Lu  1 , Danlin Yao  1 , Ling Xu  1 , Yikai Zhang  1 , Lijian Yang  1 , Jie Chen  1 , Jing Lai  1 , Zhi Yu  1 , Kanger Zhu  1 , Yangqiu Li  1   2   3
Affiliations

Higher PD-1 expression concurrent with exhausted CD8+ T cells in patients with de novo acute myeloid leukemia

Jiaxiong Tan et al. Chin J Cancer Res. 2017 Oct.

Abstract

Objective: To investigate the association between the T cell inhibitory receptor programmed death 1 (PD-1) and T cell exhaustion status in T cells from patients with de novo acute myeloid leukemia (AML) and AML in complete remission (CR).

Methods: Surface expression of PD-1 and the exhaustion and immunosenescence markers CD244 and CD57 on CD3+, CD4+ and CD8+ T cells from peripheral blood samples from 20 newly diagnosed, untreated AML patients and 10 cases with AML in CR was analyzed by flow cytometry. Twenty-three healthy individuals served as control.

Results: A significantly higher percentage of PD-1+ cells were found for CD3+ T cells in the de novo AML group compared with healthy controls. In addition, an increased level of PD-1+CD8+ T cells, but not PD-1+CD4+, was found for CD3+ T cells in the de novo AML and AML-CR samples. A higher percentage of CD244+CD4+, CD244+CD8+, CD57+CD4+ and CD57+CD8+ T cells was found in CD3+ T cells in samples from those with de novo AML compared with those from healthy controls. Strong increased PD-1+CD244+ and PD-1+CD57+ co-expression was found for CD4+ and CD8+ T cells in the de novo AML group compared with healthy controls.

Conclusions: We characterized the major T cell defects, including co-expression of PD-1 and CD244, CD57-exhausted T cells in patients with de novo AML, and found a particular influence on CD8+ T cells, suggesting a poor anti-leukemia immune response in these patients.

Keywords: Acute myeloid leukemia; PD-1; T cell exhaustion.

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Figures

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1
The percentage of PD-1+CD3+, PD-1+CD4+ and PD-1+CD8+ cells in the CD3+ T cell population from patients with de novo AML and AML-CR and healthy individuals. (A) Detection of PD-1/CD3+, PD-1+CD4+ and PD-1+CD8+ T cells in one case with AML, one case with AML in CR (AML-CR), and one healthy individual (HI) by flow cytometry; (B–D) The percentage of PD-1+CD3+ (B), PD-1+CD4+ (C), and PD-1+CD8+ (D) cells in the CD3+ T cell population from 20 patients with de novo AML, 10 cases with AML-CR, and 23 healthy individuals. Increased PD-1+CD3+ and PD-1+CD8+ T cells were found in the AML groups. PD-1, programmed death 1; AML, acute myeloid leukemia; CR, complete remission.
2
2
The percentage of CD244+ and CD57+ T cells in the CD4+ and CD8+ T cell populations of patients with de novo AML or AML-CR and healthy individuals. (A) CD244+CD4+ and CD244+CD8+ T cells; (B) CD57+CD4+ and CD57+CD8+ T cells within the CD3+ T cell population from one case with AML, one case with AML-CR and one healthy individual (HI); (C–F) CD244+CD4+, CD244+CD8+, CD57+CD4+ and CD57+CD8+ T cells within the CD3+ T cell populations from 20 cases with de novo AML, 10 cases with AML-CR and 23 healthy individuals. Increased CD244+CD4+, CD244+CD8+, CD57+CD4+ and CD57+CD8+ T cells were found in the AML group compared with HI group. AML, acute myeloid leukemia; CR, complete remission.
3
3
The percentage of PD-1+CD244+ and PD-1+CD57+ T cells in the CD4+ and CD8+ T cell populations from patients with de novo AML and AML-CR and healthy individuals. (A) The percentage of PD-1+CD244+ cells in the CD4+ T cell population in patients with AML and AML-CR and healthy individuals (HI); (B) The percentage of PD-1+CD244+ cells in the CD8+ T cell population in patients with AML and AML-CR and HI; (C) The percentage of PD-1+CD57+ cells in the CD4+ T cell population in the AML, AML-CR and HI groups; (D) Flow cytometry analysis demonstrates the percentage of PD-1+CD57+ cells in the CD8+ T cell population in the AML, AML-CR and HI groups; (E) The percentage of PD-1+CD244+ and PD-1+CD57+ cells in the CD4+ and CD8+ T cell populations in one case with AML, one case with AML-CR and a healthy individual (HI), respectively. Increased PD-1+CD244+ and PD-1+CD57+ cells in both CD4+ and CD8+ T cells were found in the AML group compared with HI group. PD-1, programmed death 1; AML, acute myeloid leukemia; CR, complete remission.
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Overview of alteration in T cell phenotypes in patients with acute myeloid leukemia (AML).
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