MicroRNA modified tumor‐derived exosomes as novel tools for maturation of dendritic cells. Issue 6 (26th October 2018)

• Record Type: Journal Article
• Authors: Taghikhani, Adeleh; Hassan, Zuhair Mohammad; Ebrahimi, Marzieh; Moazzeni, Seyyed‐Mohammad
• Is Part Of: Journal of cellular physiology. Volume 234:Issue 6(2019:Jun.)
• Page Start: 9417
• Page End: 9427
• Publication Date: 2018-10-26
• Subjects: dendritic cell maturation -- microRNA -- tumor‐derived exosomes (TEX); Physiology -- Periodicals; Cell physiology -- Periodicals; 571.6
• DOI: 10.1002/jcp.27626
• Languages: English
• ISSNs: 0021-9541

Abstract

Abstract: Tumor‐derived exosomes (TEX) are known by their immune suppression effects as well as initiation mediators in cancer progression and metastasis. Meanwhile, they are appropriate sources to induce immunity against tumor cells, as consist of tumor specific and associated antigens. The aim of the current study is modifying TEX with microRNA miR‐155, miR‐142, and let‐7i, to enhance their immune stimulation ability and induce potent dendritic cells (DC). For this, exosomes were isolated from mouse mammalian breast cancer cell line; 4T1, and subjected to miR‐155, miR‐142, and let‐7i by electroporation. Immature DCs were generated from mouse bone marrow in the presence of interleukin‐4 (IL‐4) and granulocyte‐macrophage colony‐stimulating factor (GM‐CSF). To mature DCs, lipopolysaccharide (LPS), TEX, and modified TEX were used. The expression level of miRNAs and their target genes ( IL‐6, IL‐17, IL‐1b, TGFβ, SOCS1, KLRK1, IFNγ, and TLR4 ) was determined. TEX were nanovesicles with spheroid morphology which expressed CD81, CD63, and TSG101, as exosome markers, at protein level. MHCII, CD80, and CD40 as maturation markers were assessed by flow cytometry. Overexpression of miRNAs were confirmed in exosomes and mDCs. Up and downregulation of target genes confirmed the gene network in DC maturation. We found that Let‐7i could efficiently induce the DC maturation, as well as miR‐142 and miR‐155 have enhancing effects. These findings reveal that the modified TEX would be a hopeful cell‐free vaccine for the cancer treatment. Abstract : Though there has been tremendous advancement in diagnosis, surgical, chemotherapeutic, radiotherapeutic, and specifically the immunotherapy treatment of cancer, they mostly failed in solid tumors. In this study, we tried to use tumor‐derived exosomes as a source of antigens and modified it with miR‐155, miR‐142, and Let‐7i to enhance its immunostimulatory potential as well as tumor microenvironment remodeling. It is imperative to note that we aimed to combine these properties to increase therapeutic potential of exosomes.