Table 1.
Representative examples of cellular nanovesicle-mediated immunoactive and immunosuppressive responses.
| Immunomodulatory effect | Nanovesicle source | Cellular response and function | Ref. |
|---|---|---|---|
| Immunoactivation | CD3+ T cells | Promote proliferation of CD8+ T cell | 115 |
| CD8+ T cells | Depletion of tumor stromal cells for anti-tumor effect | 116 | |
| CD4+ T cells | Inhibit proliferation of OVA-pulsed dendritic cell mediated CD4+ T cell activation; suppress the activation of CD8+ cytotoxic T lymphocytes | 119 | |
| CD4+ T cells CD8+ T cells |
Apoptosis of DCs | 120 | |
| Jurkat T cells | T cell activation | 121 | |
| CAR-T cells | Inhibition of tumor growth | 124 | |
| DCs | Activation of NK cells | 126 | |
| Facilitate secretion of IFN-γ by Th lymphocytes CD4+ and CD8+ T cell activation |
128,130,134 | ||
| Augmentation of Th1 cytokine IFN-γ production (by smaller DC-derived EVs) | 131 | ||
| NK cells | Activation of T cells; proliferation of NK cells; promote human leukocyte antigen DR isotype and expression of CD80-86 on monocytes | 139 | |
| M1-like macrophages | Polarization of M2-like macrophages toward M1 phenotype | 144,155 | |
| Produce pro-inflammatory factors and cytokines in the local microenvironment | 147,148,154 | ||
| Infected macrophages | Carry pathogen-associated molecular patterns to increase cytokine production via Toll-like receptor (TLR) activation and promote immunity | 145,146 | |
| Erythrocytes | Induce strong pro-inflammatory host response; increase the production of TNF-α, IL-6 and IL-1 from monocytes | 217 | |
| Enhance the proliferation of T cells | 218 | ||
| Platelet | Facilitate the aggregation and enhanced adhesion of monocytes to the endothelial cells; activate expression of pro-inflammation related genes in monocytes | 233 | |
| Stimulate DCs into maturation status; enhance activation of T lymphocytes | 234 | ||
| Immunosuppression | CD4+CD25+Foxp3+ Tregs | Reduce cytotoxicity of T cells | 23 |
| dnlKK2-Tregs | Blockage of cell cycle progression of cytotoxic T cells; apoptosis of T cells | 160 | |
| Tregs | Inhibit CD8+ cytotoxic T lymphocytes; attenuate production of IFN- γ and perforin; increase the amount of microRNA; decrease IL-6 and increase IL-10 production | 146 | |
| Inhibit proliferation of CD4+ T cells | 159 | ||
| Promote CD4+CD25+Foxp3+ Tregs; enhance the levels of IL-10; suppress the cytotoxic T cells | 157 | ||
| Suppress the activity of B cells | 158,160 | ||
| Attenuate antigen uptake by immature DCs | 162 | ||
| Polarization of macrophages towards the M2-like phenotype | 163 | ||
| MSCs | Reduce the level of inflammatory cytokines; M2-like macrophage polarization | 164,245 | |
| Downregulate the production of IL-17 by iNKT cells and production of TNF-α and HMGB1 by macrophages. | 171 | ||
| Upregulation of IL-10 | 174 | ||
| Attenuate activation and infiltration of CD4+ and CD8+ T cells | 174,176 | ||
| Reduce the levels of NO and pro-inflammatory cytokines from macrophages, such as IL-6 and TNF; reduce level of pro-inflammatory enzymes | 169,178 | ||
| Decrease Th17 cells accompanied by increasing number of Tregs; inhibit expression of TNF-α, IL-17, IL-6, and IL-1β | 179 | ||
| Suppress the gene of cell cycle regulator cyclin dependent kinase inhibitor 1 B to promote tumor growth | 180 | ||
| Accelerate immune escape of tumor cells; depletion of CD8+ T cells | 170,181,186 | ||
| Induce high expression of IL-6 for decreasing the proliferation of CD3+ T cells and proportion of IFN-γ+ T cells | 170 | ||
| M2-like macrophages | Attenuate the activity of B cells | 197 | |
| Reduce the inflammatory TNF-α and IL-8 from macrophages | 198 | ||
| Cancer cells | Interaction between PD-L1 and PD-1; regress the function of CD8+ T cells and promote tumor cells growth | 240,241 | |
| Macrophage migration inhibitory factor; induce release of TGF-β by Kupffer cells to remodel the extracellular matrix (ECM) in the liver | 236 | ||
| Promote expansion of CD4+CD25+FOXP3+ Tregs and the demise of antitumor CD8+ effector T cells | 237 |