Identification of myeloid-derived suppressor cells in peripheral blood of patients with non-Hodgkin lymphoma and its clinical significance

Abstract

Objective To explore the presence of myeloid-derived suppressor cells (MDSC) in patients with non-Hodgkin lymphoma (NHL) and its clinical value. Methods Peripheral blood samples were collected from 69 NHL patients and 21 healthy controls admitted in Jilin Cancer Hospital from January 2014 to February 2015. Flow cytometry was conducted to identify unique cell surface markers of MDSC using antibodies against CD11b, CD33, CD14 or HLA-DR. MDSC were enriched by immunomagnetic beads, then arginase 1 (Arg-1), inducible nitric oxide synthase (iNOS) and cyclooxygenase 2 (COX-2) in which were detected by real time-PCR. In vitro, cell proliferation assay was used to test T cell function. Statistical analysis was used to explore the correlation between MDSC and clinical features. Results There were a high level of CD11b+ CD14+ CD33+ cells in peripheral blood of NHL patients. The morphology of the cells belonged to mononuclear cells. The ratio of monocytic CD11b+ CD14+ CD33+ cells in NHL patients was higher than those in healthy controls [(42±10)%vs. (34±11)%, t= 0.300, P= 0.005]. The expressions of Arg-1, COX-2 and iNOS in CD11b+ CD14+ CD33+ and CD11b+ CD14+ CD33- cells were 0.12±0.04 vs. 1.00±0.25 (t= 6.095, P= 0.024), 3.03±0.45 vs. 1.00±0.78 (t= 7.766, P= 0.016) and 0.29±0.11 vs. 1.00±0.04 (t= 1.987, P= 0.209), respectively. In addition, the CD11b+ CD14+ CD33+ cells inhibited T cell proliferation. The levels of MDSC in patients with different international prognostic index (IPI) score were significantly different (F= 2.536, P= 0.049), but the levels of MDSC in patients with different sex, age, pathological type, stage, serum lactate dehydrogenase, physical status staging criteria and β2-microglobulin had no differences (all P < 0.05). Conclusions CD11b+ CD14+ CD33+ cells are characterized as MDSC in terms of higher level in NHL patients, expressing myeloid-specific proteins, and inhibiting T cell proliferation. The expression of MDSC is associated with IPI score, implying it might be a novel biomarker in clinical practice for NHL patients. Key words: Lymphoma, non-Hodgkin; Myeloid-derived suppressor cells; Antigens, differentiation; Biological assay