In:
Cytometry Part B: Clinical Cytometry, Wiley, Vol. 102, No. 2 ( 2022-03), p. 143-152
Abstract:
T cell dysregulation is a common event in leukemia. Recent findings have indicated that aberrant expression of immune checkpoint proteins may be associated with disease relapse and progression in acute myeloid leukemia (AML). TOX, a transcription factor in the HMG‐box protein superfamily, was found to be a potential target for immunotherapy not only in solid tumors but also in hematological malignancies. However, little is known about TOX expression and co‐expression with immune checkpoint proteins or the exhausted phenotype in the T cell subsets in AML. Thus, in this study, we analyzed TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in T cells. Methods TOX expression and co‐expression with PD‐1, Tim‐3, and CD244 in CD3+, CD4+, regulatory T (Treg), and CD8+ T cells were analyzed by multi‐color fluorescent flow cytometry in peripheral blood (PB) and bone marrow (BM) samples from patients with de novo AML and AML in complete remission (CR) and healthy individuals (HIs). Results A significantly increased percentage of TOX+CD3+, CD4+, and CD8+ T cells was found in PB from patients with de novo AML in comparison with HIs. Double‐positive TOX+CD244+, TOX+PD‐1+, and TOX+Tim‐3+ T cells markedly increased in the CD3+, CD4+, and CD8+ T cell populations in de novo AML patients compared with HIs, and similar trends were demonstrated for TOX+Tim‐3+CD3+/CD4+/CD8+ T cells in de novo AML compared with AML‐CR patients. In addition, the number of TOX+, TOX+PD‐1+, and TOX+Tim‐3+Treg cells significantly increased in de novo AML patients compared with HIs, and TOX+PD‐1+Treg cells were higher in de novo AML compared with AML‐CR patients. Moreover, TOX positively correlated with Tim‐3 expression in CD8+ and Treg cells, and a positive correlation between the expression of TOX+ CD4+ and CD244+CD4+ T cells was found. Furthermore, an increased percentage of TOX+Tim‐3+ T cells in BM was also found in de novo AML patients compared with HIs. Conclusions Increased TOX concurrent with PD‐1, Tim‐3, and CD244 in T cells may contribute to T cell exhaustion and impair their function in AML. Such exhausted T cells may be partially revised when AML patients achieve CR after chemotherapy. TOX may be considered a potential target for reversing T cell exhaustion and improving T cell function in AML.
Type of Medium:
Online Resource
ISSN:
1552-4949
,
1552-4957
DOI:
10.1002/cyto.b.v102.2
DOI:
10.1002/cyto.b.22049
Language:
English
Publisher:
Wiley
Publication Date:
2022
detail.hit.zdb_id:
2180651-2
SSG:
12
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