Abstract
Malignant cells can increase in number using immune escape mechanisms such as immune checkpoints. In this study, we evaluated the expression of an immune checkpoint programmed death 1 (PD-1) on T-cell subsets in chronic myeloid leukemia (CML). We obtained bone marrow aspirate samples from CML patients and from individuals without evidence of hematologic malignancies (controls). PD-1 expression on T-cell subsets was measured using flow cytometric analysis. PD-1 expression levels on CD8+ T-cells were significantly lower in complete hematologic response (CHR) than in controls, chronic phase, and blast phase (BP). In CML patients receiving imatinib and dasatinib, PD-1 expression levels on CD8+ T-cells were lower than that at diagnosis. PD-1 expression levels on CD8+ T-cells were positively correlated with quantitative levels of the BCR/ABL fusion gene. PD-1 expression levels on CD4+ T-cells were higher in BP than in CHR. PD-1 expression levels on CD4+ T-cells did not differ significantly according to different medications or quantitative BCR/ABL1 fusion gene levels. Low PD-1 expression on CD8+ T-cells might play a role in maintaining CHR in CML patients. Immune monitoring of PD-1 expression on CD8+ T-cells may predict the disease course. In cases of refractory disease or resistance to imatinib or dasatinib, the use of PD-1 inhibitors would be helpful.
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Data availability
The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.
Abbreviations
- AP:
-
Accelerated phase
- BP:
-
Blastic phase
- CHR:
-
Complete hematologic response
- CP:
-
Chronic phase
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Acknowledgements
The authors would like to thank Chan Hee Yoon, MT, and Sang Hee Han, MT, in the department of laboratory medicine in Asan Medical Center for technical assistance with flow cytometry. Portions of this study have been published in Abstract Book at the 24th Congress of the European Hematology Association, Amsterdam, The Netherlands, on June 13–16, 2019 [23].
Funding
This study was supported by a Grant (2016–635) from the Asan Institute for Life Science, Asan Medical Center, Seoul, Korea.
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CP and YC designed the study, and ML wrote the paper. ML and EY carried out the data management and analysis. SJ, CS, ES, EC, and JL provided study materials or patients. All authors have agreed with the final version of the paper.
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This study was approved by the institutional review board of Asan Medical Center (Approval number: 20161087) and was performed in accordance with the Declaration of Helsinki.
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Lee, M.Y., Park, CJ., Cho, YU. et al. Differences in PD-1 expression on CD8+ T-cells in chronic myeloid leukemia patients according to disease phase and TKI medication. Cancer Immunol Immunother 69, 2223–2232 (2020). https://doi.org/10.1007/s00262-020-02617-5
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DOI: https://doi.org/10.1007/s00262-020-02617-5