Table 3.
Summary for therapeutic applications of IEXs
| Exosome source | Mediator | Target cell | Mediator target | Type of disease | Therapeutic outcomes |
|---|---|---|---|---|---|
| Dendritic cell (DC) | HSP70 | Gastric cancer cell line | N/A | Gastric cancer | ↑ Apoptosis and ↓ proliferation in gastric cancer cell line |
| M1 macrophages | miR-let-7a-5p | Lung cancer cells | BCL2-like protein 1 (BCL2-L1), insulin-like growth factor 1 receptor (IGF1R), mitogen-activated protein kinase 8 (MAPK8), and Fas | Lung cancer | ↑ Autophagy and apoptosis in lung cancer cells |
| NK cell | DNAX-1 accessory molecule (DNAM1) | NALM-18 cell line | PVR and Nectin-2 | Acute lymphoblastic leukaemia |
1. Disrupts the tumor cell membranes integrity 2. ↑ Apoptosis in lung cancer cells |
| TWEAK activated macrophages | miR-7 | Ovarian cancer cells | EGFR/AKT/ERK1/2 signaling pathway | ovarian cancer | ↓ Metastasis |
| CD8+ T cells | miR-298–5p | Tumor-derived MSCs | cAMP/PKA-mediated manner | pancreatic cancer |
1. Kill tumour-derived MSCs 2. ↓ Metastasis |
| M1 macrophage | HOTTIP | Tumor cells | TLR5/NF-κB signaling pathway | HNSCC |
1. Prevents proliferation, migration, and invasion but induces apoptosis of cancer cells 2. Induce monocytes polarization to the M1 antitumor phenotype |
| NK cell | miR-186 | Tumor cells | TGF-β1-dependent manner | Neuroblastoma |
1. ↑ Apoptosis and ↓ proliferation in tumor cell 2. ↓ Immune escape in high-risk neuroblastoma patients |
| IFN-γ-induced DCs | miR-219, miR-9, miR-17–92 | Oligodendrocyte, brain resident cells | N/A | Multiple Sclerosis |
1. ↑ proliferation and differentiation of oligodendrocyte progenitor cells 2. ↑ Antioxidant activity of microglia 3. Modulating the inflammatory environment |
| Immature DCs | N/A |
B lymphocytes, T lymphocytes, |
Suppress the anti-AchR antibody-producing B cells and AchR specific T cells responses | Myasthenia Gravity |
1. ↓ Serum levels of anti-AchR, IgG1, and IgG2b 2. Shift T cell responses from Th1/Th17 to Th2/Treg |
| Myeloid-derived suppressor cells (MDSCs) | Arginase-1 (Arg-1) | TCD4+ cells | Conversion of arginine to ornithine and urea | Dextran sodium sulfate (DSS)-induced colitis |
1. ↓ the number of Th1 cells 2. ↑ the number of Treg cells 3. ↓ IFN-γ and TNF-α level in serum |
| Regulatory T cells | CTLA-4 and CD25 | TCD4+ cells | Suppress T cell activation (by CTLA-4), removing IL-2 from the environment (by CD25) | Tissue transplant |
1. ↑ Renal allografts’ long-term survival 2. Suppresses T cell proliferation |
| M1 macrophage | miR-29a, 29b, and 29c | Huh7 cells | N/A | Hepatitis C virus (HCV) infection | ↑ Anti-HCV immunity |
| LPS activated mature CD8+ DCs | MHC-1 and ICAM-1, microbial TLR ligands | DCs | LFA-1-ICAM-1 interaction, transfer the processed antigen and the peptide-MHC complex | Infectious diseases |
1. ↑ Number of activated DCs 2. ↑ Production of inflammatory cytokines 3. ↑ NK cell function 4. ↑ Differentiation of CD4+ T cells into Th1 |
| DCs and macrophages | miR-155 | Macrophages | NF-κB signaling pathway | Helicobacter pylori infection |
1. ↑ Inflammatory cytokines such as TNF-a, IL-6, IL-23 2. ↑ Costimulatory molecules such as CD40, CD63, CD81, and MHC-I |
| Mast cells | FC𝜀R1 | B lymphocyte | Free IgE | Asthma and allergies | ↓ Concentration of IgE |
| M2 macrophage | miR-370 | Airway epithelial cells (AECs) | FGF1/MAPK/STAT1 signaling axis | Asthma |
1. ↓ Cell apoptosis 2. ↓ Pulmonary fibrosis 3. ↓ OVA-induced inflammation in mice and ectopic hyperplasia in AECs 4. ↓ Number of granulocytes, such as neutrophils and eosinophils 5. ↓ Levels of IL-1β, IL-6, TNF-α, and MCP-1 |
ICAM-1 Intercellular adhesion molecule 1, APAF1 Apoptotic peptidase activating factor 1, PTEN Phosphatase and tensin homolog, NF-κB Nuclear factor-kappa B, NK cell Natural killer cells, TNF-α Tumor necrosis factor-alpha, IL Interleukin, MCP-1 Monocyte Chemoattractant Protein-1, OVA Ovalbumin, MHC Major histocompatibility complex, TLR Toll-like receptor, AchR Acetylcholine receptor, TGF-β1 Transforming growth factor-beta 1, N/A Not applicable