microRNA modified tumor‐derived exosomes as novel tools for maturation of dendritic cells

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 curren...

Full description

Saved in:
Bibliographic Details
Published in:Journal of cellular physiology 2019-06, Vol.234 (6), p.9417-9427
Main Authors: Taghikhani, Adeleh, Hassan, Zuhair Mohammad, Ebrahimi, Marzieh, Moazzeni, Seyyed‐Mohammad
Format: Article
Language:English
Subjects:
Animals
Antigen (tumor-associated)
Antigens
Bone marrow
Breast cancer
Cancer
Cancer vaccines
CD40 antigen
CD63 antigen
CD80 antigen
CD81 antigen
Cell Death - genetics
Cell Differentiation
Cell Line, Tumor
Cell Proliferation - genetics
Cytokines - metabolism
dendritic cell maturation
Dendritic cells
Dendritic Cells - cytology
Electroporation
Exosomes
Exosomes - metabolism
Flow cytometry
Gene expression
Gene Expression Regulation, Neoplastic
Gene Regulatory Networks
Genes
Immunity
Interleukins
Leukocytes (granulocytic)
Lipopolysaccharides
Macrophages
Markers
Maturation
Metastases
Mice
microRNA
MicroRNAs
MicroRNAs - genetics
MicroRNAs - metabolism
miRNA
Morphology
Neoplasms - genetics
Proteins
Ribonucleic acid
RNA
RNA, Messenger - genetics
RNA, Messenger - metabolism
T-Lymphocytes - metabolism
TLR4 protein
Toll-like receptors
Tumor cells
Tumors
tumor‐derived exosomes (TEX)
Vaccines
γ-Interferon
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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. 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.
ISSN:0021-9541
1097-4652
DOI:10.1002/jcp.27626