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

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 and 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 and 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 gene was positively correlated with gene and highly co-expressed and 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-1Foxp3 γδ T cells were detected in AML patients compared with healthy individuals. More importantly, AML patients containing higher PD-1Foxp3 γδ T cells had lower OS, which might be a potential therapeutic target for leukemia immunotherapy.

CONCLUSION

A significant increase in the PD-1Foxp3 γδ T cell subset in AML was associated with poor clinical outcome, which provides predictive value for the study of AML patients.