Table 1 The content of tumor-derived exosomes (TDEs) and their effects on developmental stages of DCs
| Exosome content | Mechanism of Action | Ref |
|---|---|---|
| Inhibition of DCs Differentiation | ||
| Cox-2, PGE2, TGF-b1, IL-6, HSP-70, and HSP-72 | Promoting the polarization of myeloid-derived suppressor cells (MDSCs), mainly through the STAT-3 pathway | [24,25,26,27,28,29, 31,32,33, 35,36,37,38] |
| Glycolytic Enzymes | Increasing ATP and lactic acid levels and enhancing MDSCs population | [18, 42,43,44,45] |
| HLA-G | Blocking monocyte-derived DCs differentiation | [39] |
| Inhibition of DCs Maturation | ||
| Galectin-9 and TIM-3 | Interacting with TIM-3 on DCs and reducing nucleic acid sensing | [51,52,53] |
| CD-47 | Reducing phagocytosis by interacting with SIRP-a on DCs | [54,55,56,57,58,59,60] |
| S100A9 | Downregulating CD83, CD86, IL-12 and IL-15 expression levels | [63,64,65,66,67] |
| TGF-b1 | Induction of TGF-b1 secretion by DCs | [9, 68, 73, 74] |
| Lactate dehydrogenase | Increasing ATP and lactate levels in tumor microenvironment | [43,44,45, 75, 76] |
| Inhibition of DCs Function | ||
| STAT3 activators | Reducing the levels of MHC and CD83 and CD86 molecules | [31, 34, 80] |
| PD-L1 | Inducing PD-1 expression and transferring of negative signals | [12, 82,83,84,85,86,87,88] |
| IDO |
- Decreasing the levels of CD40, CD83, CD86 and MHC molecules - Degrading tryptophan into kynurenine - Kynurenine-meditated increase of IDO expression on DCs | [93, 95,96,97] |
| L-arginase (ARG1) |
-Impedes the DCs-mediated T cells priming in regional lymph nodes - Reduces arginine level in tumor microenvironment, resulting in lower expression of MHC molecules | [24, 98,99,100] |
| PGE and TGF-b1 | Increasing CD73 expression on DCs, resulting in increased levels of inhibitory adenosine in tumor site | [16, 24, 104, 105] |
| Lipids | Accumulating lipids in DCs, interfering with their antigen-presentation function | [106,107,108,109] |