Prognostic significance of PD-1 expression on peripheral blood CD4+ T cells in patients with newly diagnosed chronic lymphocytic leukemia

Abstract

Introduction: Recent studies in a mouse model of chronic lymphocytic leukemia (CLL) demonstrated that inhibition of the programmed death receptor 1 (PD-1)-PD-L1 axis resulted in correction of leukemia-induced CD8+ T cell-related immune dysfunction and protected mice against CLL development. However, it remains unclear whether CLL development and progression can be also associated with CD4+ T cells expressing PD-1. Objectives: We aimed to analyze whether a quantitative assessment of CD4+PD-1+ T cells performed at the time of diagnosis can have prognostic significance in patients with CLL. Patients and Methods: We examined 56 patients with newly diagnosed CLL at different stages of the disease. The quantitative assessment of PD-1-expressing CD4+ T cells was performed in all patients, using multicolor flow cytometry. Results: We demonstrated that CLL patients with an advanced (high and intermediate risk) stage had a significantly higher number of CD4+PD-1+ T cells compared with subjects with low-grade disease. Importantly, we showed that the number of PD-1-expressing CD4+ T cells in the peripheral blood of patients referred for immediate treatment due to the advanced stage of the disease was significantly higher compared with subjects on watchful waiting. Finally, we found that treatment-naive patients with higher numbers of CD4+PD-1+ T cells at baseline showed a significantly shortened time to the first treatment compared with patients with a low number of CD4+PD-1+ T cells. Conclusions: Our study showed that the quantative assessment of CD4+PD-1+ T cells in peripheral blood using flow cytometry can facilitate prognostication of patients with newly diagnosed CLL.