Table 3.
Influences of cancer cell-derived EVs on recipient cells.
| Recipient Cells | Influences | Model | Refs. |
|---|---|---|---|
| MSCs | ↑ Differentiation to proangiogenic myofibroblasts ↑ Differentiation to pro-invasive myofibroblasts |
In vitro | [125,126] |
| Fibroblasts (CAF) | ↑ Fibroblast differentiation into CAFs ↑ Create premetastatic niche |
In vitro In vivo |
[127,128] |
| Epithelial cells | ↑ Initiate carcinogenic EMT | In vitro | [6,28] |
| Blood endothelial cells (BEC) | ↑ Reprogram normal endothelial cells to TECs ↑ Promote tumor angiogenesis ↑ Destruct endothelial barrier ↑ Extravasation of tumor cells and EVs ↑ Intravasation and metastasis of tumor cells and EVs ↑ Promote premetastatic niche formation |
In vivo, In vitro |
[129,130] |
| Monocytes Macrophages (TAM) |
↑ Induce immunosuppressive M2 polarization ↑ Expression of IL-10, CXCR4, and CCL2 ↑ Induce chemoresistance ↑ Initiate premetastatic niche formation ↓ Suppress NLRP3 inflammasome activity |
In vitro, Ex vivo |
[131,132] |
| Neutrophils (TAN) | ↑ Induce N2 polarization ↑ Promote cancer cell migration |
In vitro, In vivo |
[133] |
| Dendritic cells (DC) | ↓ Block myeloid precursor cells differentiation to DCs ↓ Induce DC apoptosis ↓ Decrease CD4+ IFN-γ+ Th1 differentiation ↑ Increase the rate of Treg |
In vitro | [134] |
| Lymphantic endothelial cells (LEC) |
↑ Lymphatic remodeling ↑ Lymphangiogenesis ↑ Immunosuppression ↑ Premetastatic niche formation ↑ Lymph node metastasis |
In vitro In vivo |
[135,136] |
| Killer T cells | ↓ Inhibit proliferation and differentiation ↓ Induce apoptosis |
Patient samples In vitro |
[137] |
| Treg cells (Immunosuppressive) |
↑ Promote the differentiation and proliferation | In vitro | [138] |
| MDSCs (Immunosuppressive) |
↑ Promote MDSC differentiation ↑ Expression of Cox2, IL-6, VEGF, and arginase-1 ↓ Decrease antitumor immunotherapy efficacy |
In vivo | [139,140] |
| Natural Killer (NK) cells | ↓ Downregulate NKG2D expression | In vitro | [141,142] |
CAF, cancer-associated fibroblast; CTL, cytotoxic T lymphocytes; EMT, epithelial-to-mesenchymal transition; MDSC, myeloid-derived suppressor cells; MSC, mesenchymal stem cell; TAM, tumor-associated macrophage; TAN, tumor-associated neutrophils; TEC, tumor vascular endothelial cells.