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.