CD14−CD10−CD45+HLA-DR−SSC+ neutrophils may be granulocytic myeloid-derived suppressor cell–like cells and relate to disease progression in non-Hodgkin's lymphoma patients

Abstract

We explored the frequency of CD14⁻CD10⁻CD45⁺HLA-DR⁻SSC⁺⁺ neutrophils (CD10⁻ neutrophils) in patients with non-Hodgkin's lymphoma (NHL), and their immunologic characteristics and clinical significance. Patients with NHL who were newly diagnosed (NDP; n = 33), in remission (RMP; n = 28) and relapsed (RLP; n = 29) were included, and 47 volunteers were recruited as healthy controls (HCs). The frequency of CD10⁻ neutrophils in the peripheral blood from HC and patients with NHL was detected. CD10⁻ and CD10⁺ neutrophils were sorted, and their cytology was analyzed. CD3⁺ T cells were also isolated and cultured with the autologous CD10⁻ or CD10⁺ neutrophils, after which the proliferation and death rates of T cells were determined. The levels of arginase-1 (Arg-1) and reactive oxygen species (ROS) in CD10⁺ or CD10⁻ neutrophils were examined. Few CD10⁻ neutrophils were detected in HCs but were significantly elevated in patients with NHL, especially in NDP and RLP. In addition, CD10⁻ neutrophils in NDP with advanced stage and high risk were markedly higher than those in NDP with limited stage and low risk. In RMP and RLP, the relapse-free survival and overall survival in patients with high CD10⁻ neutrophils were shorter than those with low CD10⁻ neutrophils. CD10⁻ neutrophils from patients with NHL, which mainly consist of immature neutrophils, inhibit T-cell proliferation and facilitate T-cell death. Furthermore, a significant increase was observed in Arg-1 expression, along with an increase to a certain extent in ROS. CD10⁻ neutrophils in patients with NHL have characteristics of myeloid-derived suppressor cells and may be related to disease progression and poor prognosis.