Table 1 Regulation of immune responses by immunostimulatory factors contained in EVs.

From: Extracellular vesicles and immunogenic stress in cancer

Immunostimulatory factors contained in EVs

Targeted immune cells

Mechanism of action

Reference

ANXA2

Macrophages

Stimulate the activation of the STAT3, p38, and NF-κB pathways in and the enhanced secretion of TNFα and IL6.

[57]

ATP

CD11b + CD11c + Ly6C high cells

Promote the differentiation of CD11b+CD11c+Ly6Chigh cells into mature bona fide DCs.

[66,67,68]

  

Upregulate the productions of IL-1β and stimulate the activation of CTL responses.

[69, 70]

HMGB1

DCs

Promotes the activation of CD4+ T cells by stimulating the cross-presentation of cancer cell neoantigens to the immune system by DCs.

[38]

 

TIM-1+Breg cells

Stimulated the expansion of the TIM-1+Breg cells through the mitogen-activated protein kinase (MAPK) and Toll-like receptor (TLR) 2/4 pathways.

[39]

Ceramides

DCs

Induce the activations of DCs and thereby enhance the function of T cells

[115]

HSPs

APCs

Increases the release of cytokines, such as IL-12, IL-6, IL-1β, and TNF-α, as well as chemokines, including RANTES, MCP-1, and MIP-1.

[102, 103]

 

DCs NK cells

Induce the maturation of DC and NK cell migration by increasing the expression of CD86, CD83, CD40, and MHC class II molecules on the DC surface.

[104,105,106]

DNA

Immune cells

Stimulate the activation of type I IFN pathway by STING.

[82,83,84,85,86,87]

RNA

Macrophages

Inhibit the expression of PTEN and increase the expression of phosphorylated AKT and PD-L1 in macrophages.

[90]

 

T cells

Decreases the production of IL-2 and the ratio of CD8+ T cells but increases the number of apoptotic T cells.

[90]