MicroRNA‐155 deficiency enhances the recruitment and functions of myeloid‐derived suppressor cells in tumor microenvironment and promotes solid tumor growth |
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| Authors: | Xuemei Jia Stephen Iwanowycz Yuzhen Wang Shiang Huang Walden Ai Daping Fan |
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| Affiliation: | 1. Department of Cell Biology and Anatomy, University of South Carolina School of Medicine, Columbia, SC;2. Department of Gynecology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, China;3. Centre for Stem Cell Research and Application, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China;4. Department of Pathology, Microbiology and Immunology, University of South Carolina School of Medicine, Columbia, SC |
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| Abstract: | 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 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‐1α, a direct target of miR‐155, was increased in miR‐155 deficient MDSCs, and that the increased HIF‐1α upregulated 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. |
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| Keywords: | microRNA‐155 MDSCs tumor growth HIF‐1α chemokines |
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