PMID- 32757734 OWN - NLM STAT- MEDLINE DCOM- 20220113 LR - 20220531 IS - 1532-4311 (Electronic) IS - 0882-0139 (Linking) VI - 50 IP - 8 DP - 2021 Nov TI - Upregulation of microRNA-155 Enhanced Migration and Function of Dendritic Cells in Three-dimensional Breast Cancer Microenvironment. PG - 1058-1071 LID - 10.1080/08820139.2020.1801721 [doi] AB - Background: Dendritic cells (DCs) play an essential role in the induction and regulation of immune responses, including the activation of effector T lymphocytes for the eradication of cancers. However, the tumor microenvironment (TME) often leads to DCs dysfunction due to their immature state. MicroRNA-155 (miR-155) has emerged as a typical multifunctional gene regulator associated with immune system development and immune cell activation and differentiation.Methods: In this study, a three-dimensional TME model that closely mimics the microenvironment of breast cancer was prepared. MiR-155 overexpression and control vectors were constructed using lentivirus. The relative expression of miR-155 was determined by qRT-PCR. Cell viability, antigen uptake and cell surface marker expression were analyzed by live-dead staining and flow cytometry. The migration ability of bone marrow-derived DCs (BMDCs) was qualified by transwell assay. A mixed lymphocyte culture assay was used to assess T cell-specific proliferation. Cytokine levels were determined by ELISA.Results: We found that the expression of miR-155 in DCs was inhibited by the TME. Furthermore, upregulation of miR-155 enhanced the migration ability, uptake of antigen and elevated the expression of the mature DCs markers CD80 and MHCII. More importantly, overexpression of miR-155 in DCs significantly induced T cell proliferation and IFN-gamma and IL-2 secretion.Conclusion: MiR-155 is a potential molecular regulator that may improve the efficacy of DCs-based tumor immunotherapy. FAU - Yang, Pengxiang AU - Yang P AD - Key Laboratory of Neuroregeneration of Jiangsu and Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, China. AD - Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, China. FAU - Cao, Xingjian AU - Cao X AD - Medical Research Center, Affiliated Hospital 2 of Nantong University, the First People's Hospital of Nantong, Nantong, China. FAU - Cai, Huilong AU - Cai H AD - Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, China. FAU - Chen, Xiang AU - Chen X AD - Medical Research Center, Affiliated Hospital 2 of Nantong University, the First People's Hospital of Nantong, Nantong, China. FAU - Zhu, Yihua AU - Zhu Y AD - Medical Research Center, Affiliated Hospital 2 of Nantong University, the First People's Hospital of Nantong, Nantong, China. FAU - Yang, Yue AU - Yang Y AD - Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, China. FAU - An, Weiwei AU - An W AD - Institute of Cancer Prevention and Treatment, Heilongjiang Academy of Medical Science, Harbin Medical University, Harbin, China. FAU - Jie, Jing AU - Jie J AD - Medical Research Center, Affiliated Hospital 2 of Nantong University, the First People's Hospital of Nantong, Nantong, China. LA - eng PT - Journal Article DEP - 20200805 PL - England TA - Immunol Invest JT - Immunological investigations JID - 8504629 RN - 0 (MIRN155 microRNA, human) RN - 0 (MicroRNAs) SB - IM MH - *Breast Neoplasms/genetics MH - Cells, Cultured MH - Dendritic Cells MH - Female MH - Humans MH - *MicroRNAs/genetics MH - Tumor Microenvironment MH - Up-Regulation OTO - NOTNLM OT - T cells activation OT - Three-dimensional culture OT - dendritic cells OT - microRNA-155 OT - tumor microenvironment EDAT- 2020/08/08 06:00 MHDA- 2022/01/14 06:00 CRDT- 2020/08/08 06:00 PHST- 2020/08/08 06:00 [pubmed] PHST- 2022/01/14 06:00 [medline] PHST- 2020/08/08 06:00 [entrez] AID - 10.1080/08820139.2020.1801721 [doi] PST - ppublish SO - Immunol Invest. 2021 Nov;50(8):1058-1071. doi: 10.1080/08820139.2020.1801721. Epub 2020 Aug 5.