Table 1.
Tumor-derived EVs induce alterations of immune-related molecules in T cells
| Tumor types/EV sources | EV cargoes | Targeted T cell types | Changes of cytokines and immune-related molecules in T cells | T cell functional changes | References |
|
Colorectal cancer DLD-1, WiDr cells |
TGF-β1 | Jurkat cell; CD4+ cells | FoxP3, LAG3, IL-10, PRF1, and GZMB ↑ | EVs containing TGF-β1 inhibit T cell growth and promote Treg cell development. | 183 |
| Plasma of patients | FasL, TRAIL | Activated CD8+ T cells | NA | FasL and TRAIL in EVs induce T cell apoptosis. | 78 |
|
Prostate cancer DU145 and PC3 |
PGE2 | CD4+ T cells; | IL-2 and TNF-α ↓ Adenosine ↑ |
Exosomal PGE2 contributes to CD73 induction in DCs; suppress T cell response and function. | 65 73 82 |
|
Melanoma MEL624; B16-F10; WM9 cells |
PD-L1 | CD8+ T cells | IFN-γ, IL-2, and TNF-α ↓ | Exosomal PD-L1 inhibit T cell proliferation and cytotoxicity. | 74 |
|
Glioma UPN933 cells; blood of patients |
NA | Jurkat cell; PBMC; T cells | IL-2, IFN-γ, IL-4, IL-5, IL-17, TNF-α, GM-CSF ↓ IL-6, IL-1, G-CSF ↑ |
Decrease T cell activation and affect cytokine output. | 184 |
|
Head and neck cancer Tu167 CGM; HN60; SCC0209 |
Galectin-1 | CD8+ T cells | IFN-γ, CD27, CD28 ↓ | Loss of CD27 and CD28 expression; suppress T cell proliferation and induce suppressor T cell phenotype. | 185 |
| PCI-13 | NA | Activated CD4+ and CD8+ T cells; Treg cells | PD-L1, CTLA-4, IL-10, COX2, FOXP3, FasL ↑ | Regulate expression of immune function-related genes in T cell subsets. | 186 |
| Plasma of patients | NA | CD8+ T cells | NA | CD45– exosomes induce CD39+ Treg differentiation and CD8+ T cell apoptosis. | 85 |
| Plasma of patients | CD39, CD73 | CD4+ CD39+ Treg cells | 5′‐AMP and purines ↑ | CD3– exosomes promote production of adenosine in Treg cells. | 126 |
|
Oral squamous cell carcinoma Cal-27; SCC-9 |
HSP70 | γδ T cells | IFN-γ, TNF-α, GZMB, perforin ↑ | Induce γδ T cell cytotoxicity, expansion and proliferation. | 100 |
| Sera of patient | FasL | Jurkat cells and activated T cells | TCR chain ↓ | Exosomal FasL induces T cell apoptosis. | 77 |
|
Breast cancer MCF7 |
CD73, CD39 | CD4+ T cells | IL-2, TNF-α ↓ Adenosine ↑ |
Exosomal CD73 and CD39 suppress T cell response. | 65 |
|
Nasopharyngeal carcinoma TW03; C666; CNE2 |
miR-24–3 p; | CD4+ and CD8+ T cells | IL-1β, IL-6, IL-10 ↑ IFN-γ, IL-2, IL-17, FGF11 ↓ |
Exosomal miRNAs inhibit T cell proliferation and Th1 and Th17 differentiation; induce development of FOXP3+ Treg cells. | 63 61 |
| Plasma of patients, C15 and C17 cells | CCL20, Galectin-9 |
CD4+, CD8+, and Treg cells | TNFRSF4, SELL, ICAM1, CCR6, TNF, GZMB, TGFβ1, IL10, IL2, IL15 ↑ | Exosomal CCL20 promotes Treg cell recruitment; exosomal galectin-9 induces T cell apoptosis. | 81 96 |
|
Pancreatic cancer BxPC‐3 cell |
NA | CD8+ T cells | PERK, ATF4 and P-eIF2α ↑ | Induce ER-stress and p38 dependent T cell apoptosis and cytotoxicity. | 79 |
|
Ovarian cancer Ascites of patient |
TGF-β1, IL-10 | CD3+ CD4+ T cells | FasL, IL-10, TGF-β1, CTLA-4, GZMB and perforin ↑ | Promote proliferation of Treg and convert CD4+ T cells to CD4+CD25+ Treg cells; up-regulate Treg suppressor functions. | 93 |
| Skov-3 cell line, ascites of patient | Arginase-1 | CD4+ and CD8+ T cells | CD3ζ ↓ | Increased arginase in EVs suppresses proliferation and immune response of CD4+ and CD8+ T cells. | 64 |
|
Hepatocellular carcinoma Serum of patients |
14-3-3ζ | CD8+ T cells | PD-1, TIM-3, LAG3, CTLA-4 ↑ | Exosomal 14-3-3ζ induces exhausted phenotype of T cells; impaires the functions, proliferation and activation of T cells. | 95 |
| Hepa1-6, H22, H7402 cells and HepG2 cells | SALL4/miR-146a-5p | CD3+ T cells | IL-2, IFN-γ, TNF-α ↓ PD-1, TIGIT, CTLA-4 ↑ |
Exosomal SALL4 and miRNA promote T cell exhaustion and inhibit T cell immune response. | 108 |
|
Lung cancer Plasma of patients, A549, PC9, and 95D cells |
circRNA- 002178 | CD8+ T cells | PD-1 ↑ | circRNA in exosomes induces T cell exhaustion. | 67 |
ATF4, activating transcription factor 4; CCR6, C-C motif chemokine receptor 6; circRNA, circular RNA; COX2, cyclooxygenase-2; CTLA-4, cytotoxic T-lymphocyte-associated protein 4; DCs, dendritic cells; EVs, extracellular vesicles; FGF11, fibroblast growth factor 11; FOXP3, forkhead box P3; G-CSF, granulocyte colony-stimulating factor; GM-CSF, granulocyte-macrophage colony-stimulating factor; GZMB, granzyme B; ICAM1, intercellular adhesion molecule 1; IFN-γ, interferon gamma; IL, Interleukin; LAG3, lymphocyte-activation gene 3; miRNA, microRNA; NA, not available; PD-1, programmed death-1; PD-L1, programmed cell death ligand 1; P-eIF2α, phosphorylation of eukaryotic initiation factor-2α; PERK, PKR-like ER kinase; PRF1, perforin 1; SCC, squamous cell carcinoma; SELL, selectin L; TGF-β, transforming growth factor beta; TIM3, T-cell immunoglobulin and mucin-domain containing-3; TNF-α, tumor necrosis factor; TNFRSF4, TNF receptor superfamily member 4; Treg, regulatory T cell.