Higher frequency of the CTLA-4 + LAG-3 + T-cell subset in patients with newly diagnosed acute myeloid leukemia.

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.