Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis
Abstract Objectives T cells play an essential role in controlling the development of B‐cell lymphoproliferative disorders (BLPDs), but the dysfunction of T cells in BLPDs largely remains elusive. Methods Using multiplexed flow cytometry, we quantified all major subsets of CD4+ helper T cells (Th) an...
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Wiley
2020-01-01
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Series: | Clinical & Translational Immunology |
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Online Access: | https://doi.org/10.1002/cti2.1105 |
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doaj-45715107bf8143e3891426e8a28a4975 |
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record_format |
Article |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shuhua Yi Yu Zhang Wenjie Xiong Weiwei Chen Zhaohua Hou Yang Yang Yuting Yan Yunbo Wei Rui Cui Huijun Wang Zhen Yu Heng Li Zengjun Li Wei Liu Rui Lv Tingyu Wang Kun Ru Dehui Zou Minglei Shu Lugui Qiu Di Yu |
spellingShingle |
Shuhua Yi Yu Zhang Wenjie Xiong Weiwei Chen Zhaohua Hou Yang Yang Yuting Yan Yunbo Wei Rui Cui Huijun Wang Zhen Yu Heng Li Zengjun Li Wei Liu Rui Lv Tingyu Wang Kun Ru Dehui Zou Minglei Shu Lugui Qiu Di Yu Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis Clinical & Translational Immunology B‐cell lymphoproliferative disorders indolent prognosis T‐cell immunological signature |
author_facet |
Shuhua Yi Yu Zhang Wenjie Xiong Weiwei Chen Zhaohua Hou Yang Yang Yuting Yan Yunbo Wei Rui Cui Huijun Wang Zhen Yu Heng Li Zengjun Li Wei Liu Rui Lv Tingyu Wang Kun Ru Dehui Zou Minglei Shu Lugui Qiu Di Yu |
author_sort |
Shuhua Yi |
title |
Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis |
title_short |
Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis |
title_full |
Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis |
title_fullStr |
Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis |
title_full_unstemmed |
Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosis |
title_sort |
prominent immune signatures of t cells are specifically associated with indolent b‐cell lymphoproliferative disorders and predict prognosis |
publisher |
Wiley |
series |
Clinical & Translational Immunology |
issn |
2050-0068 |
publishDate |
2020-01-01 |
description |
Abstract Objectives T cells play an essential role in controlling the development of B‐cell lymphoproliferative disorders (BLPDs), but the dysfunction of T cells in BLPDs largely remains elusive. Methods Using multiplexed flow cytometry, we quantified all major subsets of CD4+ helper T cells (Th) and CD8+ cytotoxic T cells (Tc) in 94 BLPD patients and 66 healthy controls. Statistics was utilised to rank T‐cell signatures that distinguished BLPDs from healthy controls and differentially presented between indolent and aggressive categories. Results By comparing with healthy controls, we found that the indolent but not aggressive type of BLPDs demonstrated a high degree of T‐cell activation, showing the increase in type I helper T (Th1) cells and follicular B‐helper T (Tfh) cells, both of which strongly associated with the enhanced differentiation of exhaustion‐like effector cytotoxic CD8+ T cells expressing PD‐1 (Tc exhaustion‐like) in indolent BLPDs. Random forest modelling selected a module of T‐cell immune signatures best performing binary classification of all BLPD patients. This signature module was composed of low naïve Th cells and high Th1, Tfh and Tc exhaustion‐like cells which efficiently identified > 85% indolent cases and was, therefore, assigned as the Indolent Dominant Module of T‐cell immune signature. In indolent BLPD patients, a strong bias towards such signatures was found to associate with clinical characteristics of worse prognosis. Conclusion Our study identified a prominent signature of T‐cell dysregulation specifically for indolent BLPDs, suggesting Th1, Tfh and Tc exhaustion‐like cells represent potential prognostic biomarkers and targets for immunotherapies. |
topic |
B‐cell lymphoproliferative disorders indolent prognosis T‐cell immunological signature |
url |
https://doi.org/10.1002/cti2.1105 |
work_keys_str_mv |
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doaj-45715107bf8143e3891426e8a28a49752020-11-25T01:15:33ZengWileyClinical & Translational Immunology2050-00682020-01-0191n/an/a10.1002/cti2.1105Prominent immune signatures of T cells are specifically associated with indolent B‐cell lymphoproliferative disorders and predict prognosisShuhua Yi0Yu Zhang1Wenjie Xiong2Weiwei Chen3Zhaohua Hou4Yang Yang5Yuting Yan6Yunbo Wei7Rui Cui8Huijun Wang9Zhen Yu10Heng Li11Zengjun Li12Wei Liu13Rui Lv14Tingyu Wang15Kun Ru16Dehui Zou17Minglei Shu18Lugui Qiu19Di Yu20State Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaQilu University of Technology (Shandong Academy of Sciences) Shandong Analysis and Test Center Laboratory of Immunology for Environment and HealthJinan ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaQilu University of Technology (Shandong Academy of Sciences) Shandong Analysis and Test Center Laboratory of Immunology for Environment and HealthJinan ChinaThe University of Queensland Diamantina Institute Translational Research Institute Brisbane QLD AustraliaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaQilu University of Technology (Shandong Academy of Sciences) Shandong Analysis and Test Center Laboratory of Immunology for Environment and HealthJinan ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaQilu University of Technology (Shandong Academy of Sciences) Shandong Artificial Intelligence Institute Jinan ChinaState Key Laboratory of Experimental Hematology National Clinical Research Center for Blood Diseases Institute of Hematology and Blood Disease Hospital Chinese Academy of Medical Sciences and Peking Union Medical College Tianjin ChinaQilu University of Technology (Shandong Academy of Sciences) Shandong Analysis and Test Center Laboratory of Immunology for Environment and HealthJinan ChinaAbstract Objectives T cells play an essential role in controlling the development of B‐cell lymphoproliferative disorders (BLPDs), but the dysfunction of T cells in BLPDs largely remains elusive. Methods Using multiplexed flow cytometry, we quantified all major subsets of CD4+ helper T cells (Th) and CD8+ cytotoxic T cells (Tc) in 94 BLPD patients and 66 healthy controls. Statistics was utilised to rank T‐cell signatures that distinguished BLPDs from healthy controls and differentially presented between indolent and aggressive categories. Results By comparing with healthy controls, we found that the indolent but not aggressive type of BLPDs demonstrated a high degree of T‐cell activation, showing the increase in type I helper T (Th1) cells and follicular B‐helper T (Tfh) cells, both of which strongly associated with the enhanced differentiation of exhaustion‐like effector cytotoxic CD8+ T cells expressing PD‐1 (Tc exhaustion‐like) in indolent BLPDs. Random forest modelling selected a module of T‐cell immune signatures best performing binary classification of all BLPD patients. This signature module was composed of low naïve Th cells and high Th1, Tfh and Tc exhaustion‐like cells which efficiently identified > 85% indolent cases and was, therefore, assigned as the Indolent Dominant Module of T‐cell immune signature. In indolent BLPD patients, a strong bias towards such signatures was found to associate with clinical characteristics of worse prognosis. Conclusion Our study identified a prominent signature of T‐cell dysregulation specifically for indolent BLPDs, suggesting Th1, Tfh and Tc exhaustion‐like cells represent potential prognostic biomarkers and targets for immunotherapies.https://doi.org/10.1002/cti2.1105B‐cell lymphoproliferative disordersindolentprognosisT‐cell immunological signature |