Yi, ShuhuaZhang, YuXiong, WenjieChen, WeiweiHou, ZhaohuaYang, YangYan, YutingWei, YunboCui, RuiWang, HuijunYu, Di2023-01-162050-0068http://hdl.handle.net/1885/282773Objectives.T cells play an essential role in controlling thedevelopment of B-cell lymphoproliferative disorders (BLPDs), butthe dysfunction of T cells in BLPDs largely remains elusive.Methods.Using multiplexed flow cytometry, we quantified allmajor subsets of CD4+helper T cells (Th) and CD8+cytotoxic T cells(Tc) in 94 BLPD patients and 66 healthy controls. Statistics wasutilised to rank T-cell signatures that distinguished BLPDs fromhealthy controls and differentially presented between indolentand aggressive categories.Results.By comparing with healthycontrols, we found that the indolent but not aggressive type ofBLPDs demonstrated a high degree of T-cell activation, showingthe increase in type I helper T (Th1) cells and follicular B-helper T(Tfh) cells, both of which strongly associated with the enhanceddifferentiation of exhaustion-like effector cytotoxic CD8+T cellsexpressing PD-1 (Tc exhaustion-like) in indolent BLPDs. Randomforest modelling selected a module of T-cell immune signaturesbest performing binary classification of all BLPD patients. This signature module was composed of low na€ıve Th cells and highTh1, 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-celldysregulation specifically for indolent BLPDs, suggesting Th1, Tfhand Tc exhaustion-like cells represent potential prognostic biomarkers and targets for immunotherapies.This work was supported by grants from the National NatureScience Foundation of China (81970187 to SY, 81800187 toYZ and 81601441 to HZ), the National Key Research andDevelopment Program of China (2016YFA0100600 to LQ and2017YFC0909003 to DY), National Science and TechnologyMajor Project from China (2017ZX09304024), NationalScience and Technology Supporting Program (2014BAI09B12to SY and LQ), Chinese Academy of Medical SciencesInnovation Fund for Medical Sciences (grants 2017-I2M-3-018, 2017-I2M-1-005 and 2016-I2M-3-013), ShandongProvincial Natural Science Foundation (ZR2016YL013 to DY,ZR2015YL005 to DY and YW, and ZR2017LH030 to YZ), the Special Foundation of Taishan Overseas Distinguished Exertsand Scholars (to DY), the Priority Research Program of theShandong Academy of Sciences (to DY), Key Lab Foundationof Shandong Academy of Sciences (to DY), Youth ScienceFunds of Shandong Academy of Sciences (2018QN005 to YZ)and the Bellberry-Viertel Senior Medical Research Fellowship(to DY)application/pdfen-AU© 2020 The Authors. Clinical & Translational Immunology published by John Wiley & Sons Australia, Ltd on behalf of Australian and New Zealand Society for Immunology IncB-cell lymphoproliferative disordersindolentprognosisT-cell immunological signature202010.1002/cti2.11052021-11-28