Jin Zhenyi, Luo Qiang, Lu Shuai, Wang Xinyu, He Zifan, Lai Jing, Chen Shaohua, Yang Lijian, Wu Xiuli, Li Yangqiu
Institute of Hematology, Medical College, Jinan University, Guangzhou, 510632, China.
Key Laboratory for Regenerative Medicine of Ministry of Education, Jinan University, Guangzhou, 510632, China.
J Hematol Oncol. 2016 Nov 18;9(1):126. doi: 10.1186/s13045-016-0353-3.
Recent data have shown that γδ T cells can act as mediators for immune defense against tumors. Our previous study has demonstrated that persisting clonally expanded TRDV4 T cells might be relatively beneficial for the outcome of patients with T cell acute lymphoblastic leukemia after hematopoietic stem cell transplantation (HSCT). However, little is known about the distribution and clonality of the TRDV repertoire in T cell receptor (TCR) of γδ T cells and their effects on the clinical outcome of patients with acute myeloid leukemia (AML). The aim of this study was to assess whether the oligoclonal expansion of TCR Vδ T cells could be used as an immune biomarker for AML outcome.
γδ T cells were sorted from the peripheral blood of 30 patients with untreated AML and 12 healthy donors. The complementarity-determining region 3 (CDR3) sizes of eight TCR Vδ subfamily genes (TRDV1 to TRDV8) were analyzed in sorted γδ T cells using RT-PCR and GeneScan. The most frequently expressed TRDV subfamilies in the AML patients were TRDV8 (86.67 %) and TRDV2 (83.33 %), and the frequencies for TRDV1, TRDV3, TRDV4, and TRDV6 were significantly lower than those in healthy individuals. The most frequent clonally expanded TRDV subfamilies in the AML patients included TRDV8 (56.67 %) and TRDV4 (40 %). The clonal expansion frequencies of the TRDV2 and TRDV4 T cells were significantly higher than those in healthy individuals, whereas a significantly lower TRDV1 clonal expansion frequency was observed in those with AML. Moreover, the oligoclones of TRDV4 and TRDV8 were independent protective factors for complete remission. Furthermore, the oligoclonal expansion frequencies of TRDV5 and TRDV6 in patients with relapse were significantly higher than those in non-recurrent cases.
To the best of our knowledge, we characterized for the first time a significant alteration in the distribution and clonality of the TRDV subfamily members in γδ T cells sorted from AML patients. Clonally expanded TRDV4 and TRDV8 T cells might contribute to the immune response directed against AML, while oligoclonal TRDV5 and TRDV6 might occur in patients who undergo relapse. While the function of such γδ T cell clones requires further investigation, TRDV γδ T cell clones might be potential immune biomarkers for AML outcome.
最近的数据表明,γδ T细胞可作为抗肿瘤免疫防御的介质。我们之前的研究表明,持续克隆性扩增的TRDV4 T细胞可能对造血干细胞移植(HSCT)后T细胞急性淋巴细胞白血病患者的预后相对有益。然而,关于γδ T细胞T细胞受体(TCR)中TRDV基因库的分布和克隆性及其对急性髓系白血病(AML)患者临床结局的影响知之甚少。本研究的目的是评估TCR Vδ T细胞的寡克隆扩增是否可作为AML预后的免疫生物标志物。
从30例未经治疗的AML患者和12名健康供体的外周血中分离出γδ T细胞。使用RT-PCR和基因扫描分析分选的γδ T细胞中8个TCR Vδ亚家族基因(TRDV1至TRDV8)的互补决定区3(CDR3)大小。AML患者中最常表达的TRDV亚家族是TRDV8(86.67%)和TRDV2(83.33%),TRDV1、TRDV3、TRDV4和TRDV6的频率显著低于健康个体。AML患者中最常克隆性扩增的TRDV亚家族包括TRDV8(56.67%)和TRDV4(40%)。TRDV2和TRDV4 T细胞的克隆扩增频率显著高于健康个体,而AML患者中TRDV1的克隆扩增频率显著较低。此外,TRDV4和TRDV8的寡克隆是完全缓解的独立保护因素。此外,复发患者中TRDV5和TRDV6的寡克隆扩增频率显著高于未复发患者。
据我们所知,我们首次对从AML患者中分离出的γδ T细胞中TRDV亚家族成员的分布和克隆性的显著改变进行了表征。克隆性扩增的TRDV4和TRDV8 T细胞可能有助于针对AML的免疫反应,而寡克隆TRDV5和TRDV6可能出现在复发患者中。虽然此类γδ T细胞克隆的功能需要进一步研究,但TRDV γδ T细胞克隆可能是AML预后的潜在免疫生物标志物。