Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia

Abstract Background 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 a...

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Main Authors: Zhenyi Jin, Qiang Luo, Shuai Lu, Xinyu Wang, Zifan He, Jing Lai, Shaohua Chen, Lijian Yang, Xiuli Wu, Yangqiu Li
Format: Article
Language:English
Published: BMC 2016-11-01
Series:Journal of Hematology & Oncology
Subjects:
Online Access:http://link.springer.com/article/10.1186/s13045-016-0353-3
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author Zhenyi Jin
Qiang Luo
Shuai Lu
Xinyu Wang
Zifan He
Jing Lai
Shaohua Chen
Lijian Yang
Xiuli Wu
Yangqiu Li
author_facet Zhenyi Jin
Qiang Luo
Shuai Lu
Xinyu Wang
Zifan He
Jing Lai
Shaohua Chen
Lijian Yang
Xiuli Wu
Yangqiu Li
author_sort Zhenyi Jin
collection DOAJ
description Abstract Background 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. Findings 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. Conclusions 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.
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spelling doaj.art-92625eea804c43b6b073ba644d24f1662022-12-22T00:43:45ZengBMCJournal of Hematology & Oncology1756-87222016-11-01911710.1186/s13045-016-0353-3Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemiaZhenyi Jin0Qiang Luo1Shuai Lu2Xinyu Wang3Zifan He4Jing Lai5Shaohua Chen6Lijian Yang7Xiuli Wu8Yangqiu Li9Institute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityKey Laboratory for Regenerative Medicine of Ministry of Education, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityInstitute of Hematology, Medical College, Jinan UniversityAbstract Background 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. Findings 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. Conclusions 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.http://link.springer.com/article/10.1186/s13045-016-0353-3Acute myeloid leukemiaγδ T cellsT cell receptorClonality
spellingShingle Zhenyi Jin
Qiang Luo
Shuai Lu
Xinyu Wang
Zifan He
Jing Lai
Shaohua Chen
Lijian Yang
Xiuli Wu
Yangqiu Li
Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
Journal of Hematology & Oncology
Acute myeloid leukemia
γδ T cells
T cell receptor
Clonality
title Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
title_full Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
title_fullStr Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
title_full_unstemmed Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
title_short Oligoclonal expansion of TCR Vδ T cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
title_sort oligoclonal expansion of tcr vδ t cells may be a potential immune biomarker for clinical outcome of acute myeloid leukemia
topic Acute myeloid leukemia
γδ T cells
T cell receptor
Clonality
url http://link.springer.com/article/10.1186/s13045-016-0353-3
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