Increased PD-1+Foxp3+ γδ T cells associate with poor overall survival for patients with acute myeloid leukemia

Abstract

Problems: 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.

Keywords: Foxp3; PD-1; acute myeloid leukemia; outcome; overall survival; γδ T cells.