Role And Mechanism Of Myeloid-derived Suppressor Cells（MDSC）in Tumor Metastasis

Background:Metastasis, or metastatic disease, is the spread of a malignant tumor cells from one organ to another not directly connected with it.Canceration related migration brings tumor cells into metastasis, and abnormal immunity make metastasis happen. To Date, many immune cells were fund exhibiting pro-tumorigenic activation and benefit tumor progression and metastasis. Myeloid-derived suppressor cells(MDSC) area heterogeneous population of cells that expand during pathological conditions(such as cancer), and that have a remarkable ability to suppress immune response.There are two subsets of MDSC, granulocytic MDSC(G-MDSC) and monocytic MDSC(M-MDSC). These cells play important roles in many steps of malignancy. Although MDSC have the ability to promote metastasis, the specific role of each MDSC subset during tumor cell metastasisremains unclear.Experimental design and results: To investigate the functions and mechanisms of G-MDSC or M-MDSC in metastasis respectively, we performed flow cytometer, cell sorting, transplantation…. We showed thatcirculating M-MDSC expansion pear to G-MDSC expansion during malignancy. We further showed thateither G-MDSC or M-MDSC promote tumor metastasis.Furthermore, we examined how G-MDSC promote tumor cell survival in circulation and showed thatcirculating G-MDSC exhibit TAN like gene expression and enhance tumor cell survival by suppressing leukocyte activation. Moreover, we examinedhow M-MDSC promote pre-metastatic niche and showed that the pulmonary recuited M-MDSC promote the expression of MMP9 in pre-metastatic niche. Finally,to determine whether M-MDSC have the potential to be a clinical indicator, we analyzed the peripheral blood of cancer patients and showed that circulating M-MDSC expand in earlier stages of liver, breast and cervical cancer patiens.Conclusions:Our findings suggest that the M-MDSCs abundance and their lung recruitment can built pre-metastatic niche and facilitate tumor cell arrest by inducing MMP9 up-regulation. Our finding also suggests that the abundance of TAN like G-MDSCin advanced cancer patients contributes to the circulatingtumor cell survival by suppressing peripheral leukocyteactivation.