Table 1.
The role of EVs in chemo-resistance and immune-modulation. Several proteins and exRNAs have been described to be involved in tumor chemo-resistance and immune-modulation.
| Biological Effect | Mechanism of Action | Cell Source | Target | References |
|---|---|---|---|---|
| Resistance to chemotherapy | Transfer of MDR-1/P-gp | Docetaxel-resistant prostate cancer | Docetaxel-sensitive prostate cancer | [59] |
| Transfer of miR-100, miR-222, miR-30a and miR-17 | Adriamycin and docetaxel-resistant breast cancer | Adriamycin and docetaxel-sensitive breast cancer | [60] | |
| Transfer of miR-21 | Platinum-resistant ovarian cancer | Platinum-sensitive ovarian cancer | [61] | |
| Transfer of miR-100-5p, miR-21 and miR-133b | Cisplatin-resistant lung cancer | Cisplatin-sensitive lung cancer | [62,63] | |
| Transfer of miR-21, which downregulates APAF1 | Stroma | Ovarian cancer | [74] | |
| Transfer of miR-146a with Snail mRNA | Cancer-Associated Fibroblasts | Pancreatic cancer | [73] | |
| Activation of the antiviral/ NOTCH3 signaling pathway | Stroma | Breast cancer | [72] | |
| Tumor immune-escape | Release of pro-inflammatory cytokines by macrophages, possibly mediated by miR-21 and miR-29a | Breast and lung cancer, melanoma | Tumor cells, fibroblasts, endothelial cells, and immune cells | [85,86,87] |
| Inhibition of dendritic cell maturation and functions, by delivering specific miRNAs (e.g., miR-203, miR-212-3p) | Renal carcinoma, pancreatic cancer, melanoma | Dendritic and T cells | [87,88,89] | |
| MDSCs activation, which leads to TGF-β-mediated suppression of T cell activity | Melanoma and colorectal carcinoma | CD14+ monocytes | [90,91] | |
| Suppression of the T-cell activity mediated by PDL-1, TGF-β, Fas ligand and TRAIL | Melanoma, colorectal, gastric and prostate cancer, head and neck squamous cell carcinoma | CD8+T cells | [92,93,94,95,96] | |
| Inhibition of NK cell cytotoxic activity, possibly mediated by MIC A ligand of NKG2D receptor | Mammary carcinoma, melanoma, cervical, head and neck, liver cancer | NK cells | [97,98,99] | |
| Enhancement of immune response | Activation of a tumor antigen-specific immune response in humans | Melanoma and non-small cell lung cancer patients-derived dendritic cells | systemic administration | [100,101] |
EVs: extracellular vesicles, MDR: multidrug resistance protein, APAF1: apoptotic protease-activating factor 1, MDSCs: myeloid-derived suppressor cells, TGF-β: trasforming growth factor-β, PDL-1: programmed death-ligand 1, TRAIL: tumor necrosis factor-related apoptosis-inducing ligand, NK: natural killer, MIC: MHC class I–related chain, NKG2D: NKG2-D type II integral membrane protein.