High TRGV 9 Subfamily Expression Marks an Improved Overall Survival in Patients With Acute Myeloid Leukemia

Abstract

BackgroundHeterogeneous T cells in acute myeloid leukemia (AML) have the combinatorial variety generated by different T cell receptors (TCRs). γδ T cells are a distinct subgroup of T cells containing TCRγ (TRGV) and TCRδ (TRDV) subfamilies with diverse structural and functional heterogeneity. Our previous study showed that clonally expanded TRDV T cells might benefit the immune response directed against AML. However, the features of the TRGV repertoire in AML remain unknown. To fully characterize the features of γδ T cells, we analyzed the distribution and clonality of TRGV I-III subfamilies (TRGV II is also termed TRVG 9), the proportions of γδ T cell subsets, and their effects on the overall survival (OS) of patients with AML.MethodsIn this study, the complementarity-determining region 3 (CDR3) size of TRGV subfamilies in γδ T cells of peripheral blood (PB) from de novo AML patients were analyzed by Genescan analysis. Expression levels of TRGV subfamilies were performed by real-time quantitative PCR. The proportions of total γδ T cells and their Vγ9+ Vδ2+ T cells subsets were detected by multicolor flow cytometry assay. We further compared the correlation among the TRGV gene expression levels, the proportion of Vγ9+ Vδ2+ T cells, and OS in AML.ResultsWe first found that the distribution pattern and clonality of TRGV subfamilies were changed. The expression frequencies and gene expression levels of three TRGV subfamilies in AML samples were significantly lower than those in healthy individuals (HIs). Compared with HIs, the proportions of total γδ T cells and Vγ9+ Vδ2+ T cells were also significantly decreased in patients with AML. In addition, patients with AML who had higher expression levels of the TRGV gene and higher proportion of Vγ9+ Vδ2+ T cells showed better OS than their counterparts. Furthermore, high expression levels of TRGV 9 and proportion of Vγ9+ Vδ2+ T cells were identified as independent protective factors for complete remission in patients with AML.ConclusionsThe restriction of TRGV usage might be related to the preference of usage of γδ T cells. Higher expression of TRGV subfamilies might be associated with better OS in AML. Higher TRGV 9 expression and increased Vγ9+ Vδ2+ T cells subfamilies might indicate a better prognosis in patients with AML.

Higher TIGIT+ γδ TCM cells may predict poor prognosis in younger adult patients with non-acute promyelocytic AML

“…Recent publications of our team and others have reported the association of a high proportion of gd T cells with improved OS (36). However, further investigation is needed to evaluate the predictive value of OS in the follow-up period.…”

“…In vitro and mouse model studies have shown the cytotoxic effects of γδ T cells on AML cells ( 35 ). Our previous study demonstrated a correlation between reduced levels of circulating γδ T cells and poor survival outcomes ( 36 ). In this study, the proportions of total γδ T cells from PB decreased in patients with AMLy-DN and AMLy-CR relative to HIs.…”

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

“…Increasing data have demonstrated the heterogeneity of γδ T cells; however, little is known about the distribution of γδ T cells and their subsets in AML patients. Our previous study found the altered expression pattern and clonality of the γδ T cell receptor repertoire and identified that some clonally expanded γδ T cell clones might be related to the immune response and clinical outcome of AML patients ( 44 , 45 ). Our previous study described the prognostic value of immune checkpoint inhibitors for AML patients by analyzing RNA-seq from the TCGA database and further validated results indicated that high expression of PD-1, PD-L1, and PD-L2 in the BM leukemia cells of AML patients correlated with poor outcomes ( 34 ).…”