Abstract | AIM: Immune suppression based on alternative regulation of immune checkpoint proteins, for example, programmed cell death receptor-1 (PD-1) and cytotoxic T lymphocyte-associated molecule-4 (CTLA-4), which results in T-cell exhaustion, contributes to cancer development and progression. In this study, we sought to characterize the distribution of CTLA-4 and T-cell lymphocyte activation gene-3 (LAG-3) expression on exhausted T cells in different T-cell subsets from patients with acute myeloid leukemia (AML). METHODS: The coexpression of CTLA-4 and LAG-3 on exhausted CD244+ and CD57+ T cells from the CD3+ , CD4+ , and CD8+ T-cell subsets in peripheral blood from 12 patients with newly diagnosed AML was analyzed by multicolor flow cytometry assay. RESULTS: A significantly higher percentage of CTLA-4+ CD3+ , CD4+ and CD8+ T cells was found in patients with AML. In addition, higher numbers of both CTLA-4+ CD244+ and CTLA-4+ CD57+ CD3+ T cells were detected. Interestingly, the increased CTLA-4+ CD244+ T cells were predominantly CD4+ T cells. In contrast, the increased CTLA-4+ CD57+ T cells primarily consisted of the CD8+ T-cell subset. A high proportion of LAG-3+ T cells was found in only a few cases with AML; however, a significantly higher proportion of coexpression of CTLA-4 and LAG-3 in the CD3+ and CD8+ T-cell subsets was detected. CONCLUSION: We for the first time observed higher CTLA-4+ CD244+ CD4+ , CTLA-4+ CD57+ CD8+ , CTLA-4+ LAG-3+ CD3+ and CTLA-4+ LAG-3+ CD8+ T cells in patients with AML, whereas the upregulated expression of LAG-3 on T cells was only found in a subset of the cases. These data may provide further information by complementing the heterogeneity of immune checkpoints expression in AML.
|
Authors | Youchun Chen, Jiaxiong Tan, Shuxin Huang, Xin Huang, Jingying Huang, Jie Chen, Zhi Yu, Yuhong Lu, Jianyu Weng, Xin Du, Yangqiu Li, Xianfeng Zha, Shaohua Chen |
Journal | Asia-Pacific journal of clinical oncology
(Asia Pac J Clin Oncol)
Vol. 16
Issue 2
Pg. e12-e18
(Apr 2020)
ISSN: 1743-7563 [Electronic] Australia |
PMID | 31612643
(Publication Type: Journal Article)
|
Copyright | © 2019 John Wiley & Sons Australia, Ltd. |
Chemical References |
|
Topics |
- Adult
- Aged
- Aged, 80 and over
- CTLA-4 Antigen
(metabolism)
- Female
- Humans
- Leukemia, Myeloid, Acute
(genetics, pathology)
- Male
- Middle Aged
- Prognosis
- T-Lymphocytes, Cytotoxic
(metabolism)
|