Circulating Granulocytic Myeloid-derlved Suppressor Cells Enhance Metastasis By Suppressing Anti-tumor Immunity

Generally,tumor metastasis includes local invasion, intravasation,circulating in the blood or lymph stream and surviving, extravasation,migrating to tissue or organs for colonization and forming secondary tumors.The main reason of tumor cell surviving in the blood and distant organs is evading the host’s immunological surveillance.During malignant progression, primary tumors rebuild leukocyte profile and suppress the host anti-tumor immune response,and myeloid-derived suppressor cells(MDSCs)emerge as an important regulator of suppressive network.MDSCs are a heterogeneous population of cellswith potent immune-suppressive activity.In cancer,two major subsets of cells that comprise MDSCs are identified: granulocytic MDSC(G-MDSC)andmonocytic MDSC(M-MDSC).Although both subsets accumulate in tumor-bearing miceand cancer patients,G-MDSC expands dramatically and represents the predominant group of MDSCs.The aim of this study is to investigate whether the circulating G-MDSC contribute to metastatic process. Here, we showed that the G-MDSC increased in the peripheral blood under the pathological condition of advanced malignancy by multicolor flow cytometry analyses. We further showed that, in mouse model, the increased circulating G-MDSC enhance tumor metastasis. Moreover, the transcriptional analyses showed that G-MDSC had a higher expression level of immune suppression gene Arg1 and i NOS, and the detection of apoptosis showed that the G-MDSC contributed to tumor survival in vitro. In conclusion, our findings suggest that the abundance of circulating G-MDSC contribute to metastasis by suppressing anti-tumor immunity.