TABLE 3.
Clinical applications of extracellular vesicles in HCC immunotherapies.
| Type of treatment | Extracellular vesicles | Target | Role | Refs |
|---|---|---|---|---|
| Engineered exosomes | PIONs@E6 | Macrophage | Promotes the polarization of M1 macrophages to enhance their immunity against HCC | Chen et al. (2021a) |
| Engineered exosomes | IL4R-Exo (si/mi) | Macrophage | Reprograms TAMs into M1-like macrophages and increases antitumor immunity | Gunassekaran et al. (2021) |
| Engineered exosomes | exoASO-STAT6 | Macrophage | Selectively silences STAT6 expression in TAMs and reprograms them to a pro-inflammatory M1 phenotype | Zuo et al. (2022) |
| DC vaccines | DEX | DC | Promotes DC recruitment and activation to induce tumor-specific immune responses | Kamerkar et al. (2022) |
| DC vaccines | DEXAFP | CD8+ T cells | Activate CD8+ T lymphocytes to elicit a strong antigen-specific immune response | Lu et al. (2017) |
| DC vaccines | DC-Dex | T cell | Stimulates naive T cell proliferation and induces T cell activation into antigen-specific cytotoxic T lymphocytes | Li et al. (2018a) |
| DC vaccines | TEX-N1ND | DC | Enhances the ability of DCs to activate T cells and improves vaccine efficiency | Zuo et al. (2020) |
| DC vaccines | TEXs | DC | Carries HCC antigens, triggers strong DC-mediated immune response | Rao et al. (2016) |
| DC vaccines | DEX | CD8+ T cells and Treg cells | Increases the number of CD8+ T cells and decreases the number of Treg cells | Zhong et al. (2020) |
| Oncolytic Viro | EVM/VSV-G Ad5-P | Not specified | Enhanced viral infection efficiency, oncolytic ability, and soluble PD-1 production | Zhang et al. (2020b) |
| ICIs | PD-L1 | Not specified | Exosomal PD-L1 gene blockade promotes T cell activity in draining lymph nodes, thereby inducing systemic antitumor immunity and memory | Poggio et al. (2019) |
| ICIs | HCC-derived exosomes | Macrophage | Exosomes derived from HCC cells treated with 0.1 mM melatonin can downregulate the expression of PD-L1 on macrophages | Cheng et al. (2017) |
| ICIs | EV-siRNA | HCC cells | Targeting β-catenin to enhance anti-PD-1 therapeutic response | Matsuda et al. (2019) |
| Others | NK-exo | HCC cells | Inhibition of serine/threonine kinase pathway-related HCC cell proliferation and promotion of caspase activation pathway-related HCC cell apoptosis | Kim et al. (2022) |
| Others | ADMSC-derived exosomes | NKT-cell | Promote NKT cell anti-tumor immunity | Ko et al. (2015) |
| Others | Irradiated tumor cells derived-sEVs | DC | Promotes the release and presentation of tumor antigens | Lin et al. (2020) |
TAMs, tumor-associated macrophages; DC, dendritic cell; DEX, DC-derived exosomes; DEXAFP, exosomes derived from AFP-expressing DCs; DC-Dex, exosomes derived from recombinant adeno-associated viral vector (rAAV)-carrying AFP -transfected DC; TEXs, Tumor cell-derived exosomes; Treg cells, regulatory T cells; TEX-N1ND, TEXs painted with the functional domain of high mobility group nucleosome-binding protein 1 (HMGN1); EVM/VSV-G Ad5-P, extracellular vesicles-mimetic encapsulated a recombinant adenovirus expressing the extracellular domain of PD1; NK-exo, natural killer cell-derived exosomes; ADMSC, adipose-derived mesenchymal stem cells; NKT-cell, natural killer T-cell.