Circulating CD14+HLA-DR−/low myeloid-derived suppressor cell is an indicator of poor prognosis in patients with ESCC

• DOI: 10.1007/s13277-015-3426-y
• Publication Date: 2015-05-13T15:51:10Z
• Authors: Haitao Huang; Guangbo Zhang; Guangbin Li; Haitao Ma; Xueguang Zhang
• Keywords: Male; Antigen Presentation; Esophageal Neoplasms; Lipopolysaccharide Receptors; HLA-DR Antigens; Middle Aged; Flow Cytometry; Lymphocyte Activation; Prognosis; 3. Good health; 03 medical and health sciences; 0302 clinical medicine; Case-Control Studies; Lymphatic Metastasis; Biomarkers, Tumor; Carcinoma, Squamous Cell; Humans; Female; Myeloid Cells; Aged; Cell Proliferation; Follow-Up Studies; Neoplasm Staging

Accumulating evidences demonstrate that a population of suppressive cells known as myeloid-derived suppressor cells (MDSCs) is key immune modulators which suppress antitumor immunity. In this study, we found that the level of circulating CD14(+)HLA-DR(-/low) cells in patients was significantly higher than that of healthy donors and was correlated with tumor burden, lymph node metastasis, and tumor, node, and metastasis (TNM) clinical stage. More importantly, we for the first time find the level of CD14(+)HLA-DR(-/low) is a biological indicator of poor prognosis through the analysis of 3-year overall survival. Furthermore, we evidenced that the proportion of CD14(+)HLA-DR(-/low) cells in the tumor metastatic tumor-draining lymph nodes (TDLNs) was notably higher compared to tumor-free TDLNs. Additionally, CD14(+)HLA-DR(-/low) cells from esophageal squamous cell carcinoma (ESCC) patients expressed dramatically increased programmed death ligand 1 (PD-L1) comparing to that from healthy control. Subsequently, blocking PD-L1 pathway by antibody could effectively reverse the suppressive effect on autologous T cell proliferation mediated by CD14(+)HLA-DR(-/low) cells in vitro. In conclusion, our data revealed CD14(+)HLA-DR(-/low) MDSCs which increase in ESCC patients is a novel poor prognostic indicator and may exert immunosuppressive properties through PD-L1/PD-1 pathway.