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microRNA-155 Deficiency Enhances the Recruitment and Functions of Myeloid-Derived Suppressor Cells in Tumor Microenvironment and Promotes Solid Tumor Growth #MMPMID25143000
Wang J; Yu F; Jia X; Iwanowycz S; Wang Y; Huang S; Ai W; Fan D
Int J Cancer 2015[Mar]; 136 (6): E602-13 PMID25143000show ga
Immune cells in tumor microenvironment play a prominent role in tumor progression and metastasis. MicroRNA-155 (miR-155) represents an important player in innate and adaptive immunity by regulating differentiation, maturation and activation of macrophages, dendritic cells, B cells and T cells. However, the role of miR-155 expression in immune cells in solid tumor development is less elucidated. Our current study showed that both B16-F10 melanoma and Lewis lung carcinoma (LLC) tumors grew much faster in bic/miR-155 knockout (miR-155?/?) mice along with an increase of myeloid-derived suppressor cells (MDSCs) accumulation in tumors, compared to that in wild-type mice. Bone marrow transplantation study showed that bone marrow miR-155 deficiency could replicate the above tumor-promoting phenotype. In vitro study demonstrated that tumor-infiltrating miR-155?/? MDSCs showed greater migration ability and expressed higher level of multiple chemokines. Furthermore, we found that the level of HIF-1?, a direct target of miR-155, was increased in miR-155 deficient MDSCs, and that the increased HIF-1? up-regulated CXCL1, CXCL3 and CXCL8 expression in MDSCs, contributing to the enhanced recruitment of miR-155?/? MDSCs to the tumors. Moreover, miR-155?/? MDSCs showed enhanced immunosuppressive and pro-angiogenic capacities. Taken together, our study, for the first time, demonstrated that miR-155 deficiency promoted solid tumor growth through increasing the recruitment of MDSCs to tumor microenvironment and enhancing the tumor-promoting functions of the recruited MDSCs. Thus, upregulating miR-155 expression in MDSCs may be developed as a therapeutic approach to halt tumor development.