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 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.