In:
Frontiers in Oncology, Frontiers Media SA, Vol. 12 ( 2022-12-15)
Abstract:
γδ T cells are essential for anti-leukemia function in immunotherapy, however, γδ T cells have different functional subsets, including regulatory cell subsets expressing the Foxp3. Whether they are correlated with immune-checkpoint mediated T cell immune dysfunction remains unknown in patients with acute myeloid leukemia (AML). Methods In this study, we used RNA-seq data from 167 patients in TCGA dataset to analyze the correlation between PD-1 and FOXP3 genes and these two genes’ association with the prognosis of AML patients. The expression proportion of Foxp3 + /PD-1 + cells in γδ T cells and two subgroups Vδ1 and Vδ2 T cells were performed by flow cytometry. The expression level of FOXP3 and PD-1 genes in γδ T cells were sorted from peripheral blood by MACS magnetic cell sorting technique were analyzed by quantitative real-time PCR. Results We found that PD-1 gene was positively correlated with FOXP3 gene and highly co-expressed PD-1 and FOXP3 genes were associated with poor overall survival (OS) from TCGA database. Then, we detected a skewed distribution of γδ T cells with increased Vδ1 and decreased Vδ2 T cell subsets in AML. Moreover, significantly higher percentages of PD-1 + γδ, Foxp3 + γδ, and PD-1 + Foxp3 + γδ T cells were detected in de novo AML patients compared with healthy individuals. More importantly, AML patients containing higher PD-1 + Foxp3 + γδ T cells had lower OS, which might be a potential therapeutic target for leukemia immunotherapy. Conclusion A significant increase in the PD-1 + Foxp3 + γδ T cell subset in AML was associated with poor clinical outcome, which provides predictive value for the study of AML patients.
Type of Medium:
Online Resource
ISSN:
2234-943X
DOI:
10.3389/fonc.2022.1007565
DOI:
10.3389/fonc.2022.1007565.s001
Language:
Unknown
Publisher:
Frontiers Media SA
Publication Date:
2022
detail.hit.zdb_id:
2649216-7