Increased PD-1(+)Foxp3(+) gamma delta T cells associate with poor overall survival for patients with acute myeloid leukemia

Problems: gamma delta T cells are essential for anti-leukemia function in immunotherapy, however, gamma delta 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 gamma delta T cells and two subgroups V delta 1 and V delta 2 T cells were performed by flow cytometry. The expression level of FOXP3 and PD-1 genes in gamma delta 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 gamma delta T cells with increased V delta 1 and decreased V delta 2 T cell subsets in AML. Moreover, significantly higher percentages of PD-1(+) gamma delta, Foxp3(+) gamma delta, and PD-1(+)Foxp3(+) gamma delta T cells were detected in de novo AML patients compared with healthy individuals. More importantly, AML patients containing higher PD-1(+)Foxp3(+) gamma delta T cells had lower OS, which might be a potential therapeutic target for leukemia immunotherapy. Conclusion: A significant increase in the PD-1(+)Foxp3(+) gamma delta T cell subset in AML was associated with poor clinical outcome, which provides predictive value for the study of AML patients.