TABLE 3.
The role of exosomes in immune regulation.
| Phenotype | Type of primary cancer | Contents in exosomes | Target organ/cells | Specific mechanism | References |
|---|---|---|---|---|---|
| Immune regulation | Lung cancer/Melanoma | Not mention exosomes | Lung resident fibroblasts | Lung resident fibroblasts producing fibronectin to recruit VEGFR1+/VLA-4+ HPCs to form cellular clusters and PMN | Kaplan et al. (2005) |
| Pancreatic ductal adenocarcinomas | MIF | Liver kupffer cells | Kupffer cell and HSCs were activated to induced the inflammatory PMN formation and recruit macrophages and granulocytes | Costa-Silva et al. (2015) | |
| Lung cancer/melanoma | RNAs | lung epithelial cells | TLR3+ lung epithelial cells increasing chemokine secretion and recruit neutrophil to form PMN | Liu et al. (2016) | |
| Non metastatic melanoma | PEDF | Lung | Recruiting monocytes Ly6Clow and promoting them differentiation into macrophage by increasing the Nr4a1 transcription factor expression; inducing macrophage M1 polarization and recruiting NK cells to prevent lung metastasis | Plebanek et al. (2017) | |
| Melanoma | — | Lung | Recruiting the Ly6Clow patrolling monocytes via the BAG6/CBP/p300-p53 axis to prevent lung metastasis | Schuldner et al. (2019) | |
| CRC | miR-934 | Liver | M2 macrophage polarization via downregulation of PTEN expression and activating the PI3K/AKT signaling pathway; activating the a CXCL13/CXCR5/NFκB/p65/miR-934 positive feedback loop | Zhao et al. (2020) | |
| CRC | ANGPTL1 | Liver | Changing Kupffer cells secretion pattern to attenuate liver metastasis | Jiang et al. (2021) | |
| Head and neck cancers | - | T/NK cells | Downregulating the NKG2D expression levels in NK cells; inducing apoptosis of CD8+ T cells; suppressing CD4+ T-cell proliferation; upregulating Treg cells suppressor functions | Ludwig et al. (2017) | |
| Pancreatic cancer | TGF-β1 | NK cells | Inducing the phosphorylation of Smad2/3 and downregulating the expression of NKG2D, CD107a, TNF-α, and INF-γ to attenuate NK cell cytotoxicity | Zhao et al. (2019) | |
| Melanomas | PD-L1 | T cells | Suppressing CD8 T cells and the immune system function | Chen et al. (2018) | |
| Melanoma/prostate cancer | PD-L1 | Lymph node; T cells | Suppressing T cell activity | Poggio et al. (2019) | |
| Wound repair | PD-L1 | T cells; epidermal cells and dermal fibroblasts | Suppressing T cell activation; the migration of epidermal cells and dermal fibroblasts was promoted | Su et al. (2020) | |
| Lung cancer/colon cancer cells | BMDCs -derived exosomal PD-L1 | T cells | Inhibiting CD8+ T cell proliferation and activation | Sun et al. (2020) |
Abbreviation: VEGFR1, vascular endothelial growth factor receptor 1; VLA-4. integrin α4β1; PMN, pre-metastatic niche; HPCs, hematopoietic progenitor cells; MIF, macrophage migration inhibitory factor; Toll-like receptors 3, TLR3; PEDF, pigment epithelium-derived factor; CRC, colorectal cancer; ANGPTL1, angiopoietin-like protein1; TGF-β1, transforming growth factor beta1; PD-L1, programmed death-ligand 1; BMDCs, bone marrow-derived cells.