Elevated levels of follicular T helper cells and their association with therapeutic effects in patients with chronic lymphocytic leukaemia

Abstract

Chronic lymphocytic leukaemia (CLL) is characterized by an abnormal expansion of mature B cells with variable progression. Follicular T helper (Tfh) cells help B cells differentiate into plasma cells or long-lived memory B cells in germinal centres (GCs). However, the role of Tfh cells in CLL is poorly understand, and whether it plays a critical role in disease progression in vivo is lacking. In this study, we investigate the dynamic change of circulating Tfh cells in peripheral blood from patients with CLL during the treatment periods to evaluate their utility to predict disease progression. Our findings revealed the expansion of circulating CD4⁺CXCR5⁺, CD4⁺ICOS⁺, CD4⁺PD-1⁺ and CD4⁺CXCR5⁺ICOS⁺PD-1⁺ (Tfh) cells but lower serum IL-21 levels and CD4⁺ T cell polarization not only to Tfh2 subtypes but also to Tfh17 subtypes in patients with CLL at pretreatment compared to patients with monoclonal B cell lymphocytosis (MBL) and healthy individuals, especially in those with advanced stage, which indicate these Tfh cells could be employed as a novel indicator for disease progression. Moreover, we observed significant correlations of Tfh17 and immunoglobulin heavy chain variable region (IGHV) mutation. Importantly, significantly decreased CD4⁺ICOS⁺, CD4⁺PD-1⁺ and Tfh cells were found after effective treatments, whereas a significantly high CD4⁺ICOS⁺, CD4⁺PD-1⁺ and Tfh cells were still found in those with progressive disease after treatments, suggesting that circulating CD4⁺ICOS⁺, CD4⁺PD-1⁺, Tfh cells could predict therapeutic effects.

Keywords: Chronic lymphocytic leukaemia; Disease progression; Flow cytometry; Follicular T helper cells; Therapeutic effects.