Table 1

Tumor-derived EVs induce alterations of immune-related molecules in T cells

Tumor types/EV sourcesEV cargoesTargeted T cell typesChanges of cytokines and immune-related molecules in T cellsT cell functional changesReferences
Colorectal cancer
DLD-1, WiDr cells
TGF-β1Jurkat cell; CD4+ cellsFoxP3, LAG3, IL-10, PRF1, and GZMB ↑EVs containing TGF-β1 inhibit T cell growth and promote Treg cell development.183
Plasma of patientsFasL, TRAILActivated CD8+ T cellsNAFasL and TRAIL in EVs induce T cell apoptosis.78
Prostate cancer
DU145 and PC3
PGE2CD4+ 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-L1CD8+ T cellsIFN-γ, IL-2, and TNF-α ↓Exosomal PD-L1 inhibit T cell proliferation and cytotoxicity.74
Glioma
UPN933 cells; blood of patients
NAJurkat cell; PBMC; T cellsIL-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-1CD8+ T cellsIFN-γ, CD27, CD28 ↓Loss of CD27 and CD28 expression; suppress T cell proliferation and induce suppressor T cell phenotype.185
PCI-13NAActivated CD4+ and CD8+ T cells; Treg cellsPD-L1, CTLA-4, IL-10, COX2, FOXP3, FasL ↑Regulate expression of immune function-related genes in T cell subsets.186
Plasma of patientsNACD8+ T cells NACD45 exosomes induce CD39+ Treg differentiation and CD8+ T cell apoptosis.85
Plasma of patientsCD39, CD73CD4+ CD39+ Treg cells5′‐AMP and purines ↑CD3 exosomes promote production of adenosine in Treg cells.126
Oral squamous cell carcinoma
Cal-27; SCC-9
HSP70γδ T cellsIFN-γ, TNF-α, GZMB, perforin ↑Induce γδ T cell cytotoxicity, expansion and proliferation.100
Sera of patientFasLJurkat cells and activated T cellsTCR chain ↓Exosomal FasL induces T cell apoptosis.77
Breast cancer
MCF7
CD73, CD39CD4+ T cellsIL-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 cellsIL-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 cellsCCL20,
Galectin-9
CD4+, CD8+, and Treg cellsTNFRSF4, 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
NACD8+ T cellsPERK, ATF4 and P-eIF2α ↑Induce ER-stress and p38 dependent T cell apoptosis and cytotoxicity.79
Ovarian cancer
Ascites of patient
TGF-β1, IL-10CD3+ CD4+ T cellsFasL, 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 patientArginase-1CD4+ and CD8+ T cellsCD3ζ ↓Increased arginase in EVs suppresses proliferation and immune response of CD4+ and CD8+ T cells.64
Hepatocellular carcinoma
Serum of patients
14-3-3ζCD8+ T cellsPD-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 cellsSALL4/miR-146a-5pCD3+ T cellsIL-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- 002178CD8+ T cellsPD-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.