Table 1.
Potential role of exosomes in improving the efficacy of HCC immunotherapies.
| Type of Treatment | Exosomes | Role | References |
|---|---|---|---|
| ICIs | PD-L1 | Administrate miR-220a/220b/429 mimics to interference with HMGB1 and RICTOR, thereby inhibiting the production of PD-L1-contaning exosomes |
[88] |
| PD-L1 | Use hemofiltration to remove the PD-L1-contaning exosomes from the bloodstream |
[91] | |
| HCC-derived exosomes | Administrate exosomes derived from HCC cells treated with 0.1 Mm melatonin, thereby downregulating the expression of PD-L1 on macrophages |
[92] | |
| miR-15a-5p | Inhibit PD-1 expression on CD8+ T cells | [31] | |
| Exosome-encapsulated small interfering RNA | Target β-catenin, thereby blocking Wnt/β-catenin signaling, which can contribute to immune evasion |
[93] | |
| DC-TEX | Combine DC-TEX and PD-1 inhibitor to enhance the efficacy of sorafenib | [96] | |
| CTLA-4, PD-1 | Use tonifying traditional Chinese medicine to treat spleen deficiency, thereby reducing the exosomal CTLA-4 and PD-1 | [85] | |
| DC vaccine | TEXs | Carry HCC antigens and trigger a strong DC- mediated immune response |
[37] |
| TEX-N1ND | Strengthen DC immunogenicity and suppress large established tumors | [99] | |
| DEX | Promote the proliferation of naïve T cells and differentiate to cytotoxic T lymphocytes |
[39] | |
| DEX-AFP | Increase the number of CD8+ T cells and reduce the number of CD25+ Foxp3+ regulatory T cells | [38] | |
| Virus vaccine | EVM/VSV-G Ad5-P | Enhance the efficacy of type V adenovirus | [101] |
| CAR-T | RN7SL1 | Co-deploy peptide antigen and enhance the efficacy of CAR-T | [104] |
| CAR-containing exosomes | Hold potential anti-tumor effects | [105] | |
| CAR-T cell-derived exosomes | Can be positive modulated by T lymphocyte activation enhancers | [106] | |
| NK cell | HSP-bearing exosomes | Elicit efficient NK cells | [109] |
| Exosomes derived from hepatoma G2 cells | Reinforce the cytotoxicity of NK cells | [110] | |
| M1 macrophage | Exosomes | Synergize with PIONs@E6 and heighten the M1 macrophages polarization |
[111] |
| Exosomes derived from M1 macrophages (IL4R-Exo) | Heighten the M1 macrophages polarization | [112] | |
| Engineered exosomes (exoASO-STAT6) | Silence STAT6 expression in tumor-associated macrophages and reprogram them to M1 phenotype |
[113] | |
| Others | miR-125b-loaded EVs | Specifically reduce HCC cell proliferation by regulating the p53 signaling pathway |
[115] |
| EVs from red blood cells | Accumulate in liver and diminish systemic toxicity of delivered drugs | [116] | |
| Mesenchymal stem cells | Homologous TEXs | Enhance the migratory capacity of bone MSCs, which have great antitumor activities | [117] |
| BMSC-derived exosomal miR-338-3p | Down-regulate EST1 and thereby inhibit HCC | [118] | |
| Adipose-derived MSCs exosomes | Promote the anti-tumor response of NKT cells | [119] | |
| Human umbilical cord MSCs exosomal miR-451a | Restrict the epithelial-mesenchymal transition of HCC cells | [120] |
Developing drugs for exosomes could enhance the efficacy of ICIs, tumor vaccines, adoptive cell therapy, and others. ICIs, immune checkpoint inhibitors; DC, dendritic cell; CAR-T, chimeric antigen receptor T; NK, nature killer; PD-L1, programmed cell death ligand 1; CTLA-4, cytotoxic-T-lymphocyte-associated protein 4; PD-1, programmed cell death protein 1; DC-TEX, TEX-pulsed DCs; DEX, DC-derived exosomes; DEX-AFP, exosomes derived from AFP-expressing DCs; EVs, extracellular vesicles; TEX, tumor-cell-derived exosomes; MSCs, mesenchymal stem cells; HCC, hepatocellular carcinoma.