AUTHOR=Kong Xueting , Zheng Jiamian , Liu Xiaxin , Wang Wandi , Jiang Xuan , Chen Jie , Lai Jing , Jin Zhenyi , Wu Xiuli 

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

JOURNAL=Frontiers in Immunology

VOLUME=13

YEAR=2022

URL=https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2022.823352

DOI=10.3389/fimmu.2022.823352

ISSN=1664-3224

ABSTRACT=<sec><title>Background</title><p>Heterogeneous 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 (<italic>TRGV</italic>) and TCRδ (<italic>TRDV</italic>) subfamilies with diverse structural and functional heterogeneity. Our previous study showed that clonally expanded <italic>TRDV</italic> T cells might benefit the immune response directed against AML. However, the features of the <italic>TRGV</italic> repertoire in AML remain unknown. To fully characterize the features of γδ T cells, we analyzed the distribution and clonality of <italic>TRGV I-III</italic> subfamilies (<italic>TRGV II</italic> is also termed <italic>TRVG 9</italic>), the proportions of γδ T cell subsets, and their effects on the overall survival (OS) of patients with AML.</p></sec><sec><title>Methods</title><p>In this study, the complementarity-determining region 3 (CDR3) size of <italic>TRGV</italic> subfamilies in γδ T cells of peripheral blood (PB) from <italic>de novo</italic> AML patients were analyzed by Genescan analysis. Expression levels of <italic>TRGV</italic> subfamilies were performed by real-time quantitative PCR. The proportions of total γδ T cells and their Vγ9<sup>+</sup> Vδ2<sup>+</sup> T cells subsets were detected by multicolor flow cytometry assay. We further compared the correlation among the <italic>TRGV</italic> gene expression levels, the proportion of Vγ9<sup>+</sup> Vδ2<sup>+</sup> T cells, and OS in AML.</p></sec><sec><title>Results</title><p>We first found that the distribution pattern and clonality of <italic>TRGV</italic> subfamilies were changed. The expression frequencies and gene expression levels of three <italic>TRGV</italic> 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<sup>+</sup> Vδ2<sup>+</sup> T cells were also significantly decreased in patients with AML. In addition, patients with AML who had higher expression levels of the <italic>TRGV</italic> gene and higher proportion of Vγ9<sup>+</sup> Vδ2<sup>+</sup> T cells showed better OS than their counterparts. Furthermore, high expression levels of <italic>TRGV 9</italic> and proportion of Vγ9<sup>+</sup> Vδ2<sup>+</sup> T cells were identified as independent protective factors for complete remission in patients with AML.</p></sec><sec><title>Conclusions</title><p>The restriction of <italic>TRGV</italic> usage might be related to the preference of usage of γδ T cells. Higher expression of <italic>TRGV</italic> subfamilies might be associated with better OS in AML. Higher <italic>TRGV 9</italic> expression and increased Vγ9<sup>+</sup> Vδ2<sup>+</sup> T cells subfamilies might indicate a better prognosis in patients with AML.</p></sec>