Table 1 EVs regulate the biogenesis of immune checkpoints.
From: Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics
Type of cancer | Origin | Cargos | Target Cells | Target Immune Checkpoints | Mechanism | impacts on cancer progression | References |
|---|---|---|---|---|---|---|---|
Hepatocellular Carcinoma | Cancer cell derived EVs | LOXL4 | M2-polarized tumor-associated macrophages | PD-L1 | Induce PD-L1 expression by activating STAT1 | Promoted the immune escape of HCC cells by inhibiting the killing ability of CD8 + T cells | |
Cancer cell derived EVs | GOLM1 | cancer cells | PD-L1 | Promote CSN5-mediated PD-L1 deubiquitination | Promotes PD-L1 stabilization | ||
macrophages/NK cells | Upregulate PD-L1 expressed by TAMs | Suppresses NK cells | |||||
cancer cells | Suppresses Rab27b diverts PD-L1 to the membrane | Increase the exosomal PD-L1 levels | |||||
M1-polarized tumor-associated macrophages derived EVs | MISP | cancer cells | PD-L1 | Upregulated phosphorylation of STAT3 | Advance immune escape of HCC cells | ||
Ovarian Cancer | M2-polarized tumor-associated macrophages derived EVs | NEAT1 | cancer cells | PD-L1 | Sponged miR-101-3p to increase translate factor ZEB1 and PD-L1 expression | Promote OC cell proliferation and CD8 + T cell apoptosis | |
Esophageal Squamous Cell Carcinoma | Cancer cell derived EVs | PIK3CB | cancer cells | PD-L1 | Promoted the transcriptional activity of the PD-L1 promoter | Promote epithelial-mesenchymal transition | |
Esophageal carcinoma stem cells derived EVs | OGT | CD8 + T cells | PD-1 | unknown | Affect the expansion and function of cytotoxic CD8 + T cells | ||
Breast Cancer | Cancer cell derived EVs | miR-106b-5p | M2-polarized tumor-associated macrophages | PD-L1 | Promote phosphorylation of PI3K downstream products by inhibiting PTEN translation | Regulate PD-L1 expression in macrophages and their polarization | |
miR-18a-5p | Promote the binding of STAT3 and PD-L1 coding gene by inhibiting PIAS3 translation | ||||||
Head and Neck Cancer | Cancer cell derived EVs | IFNGR1 | fibroblastic reticular cells | PD-L1 | Activate downstream JAK and STAT1 to promote PD-L1 transcription | Facilitate pre-metastatic niche formation and tumor metastasis in sentinel lymph node | |
Cancer cell derived EVs | miR-21-5p | cancer cells | LAG3 | Inhibit expression of LAG3 transcriptional regulatory factor early growth response protin 3 | Participate in tumor cell drug resistance and regulate epithelial-mesenchymal transition | ||
Colorectal Cancer | Colorectal cancer stem cells-derived exosomes | miR-17-5p | cancer cells | PD-L1 | Targeted inhibition of SPOP expression, limiting the binding of ubiquitin-activating enzyme to PD-L1 | Promote growth and inhibit anti-tumor immunity in CRC cells through promoting PD-L1 | |
Cancer cell derived EVs | LncRNAKcnq1OT1 | PD-L1 | LncRNAKcnq1OT1 competitively binds with MIR-30A-5P to Ubiquitin-Specific Protease 22 (USP22), thereby facilitating the cleavage of ubiquitin chains from ubiquitinated PD-L1 by USP22 | Suppress basic apoptosis rate of tumor cells | |||
Cancer cell derived EVs | miR-21-5p | M2-polarized tumor-associated macrophages | PD-L1 | Promote phosphorylation of PI3K downstream products by inhibiting PTEN translation | Regulate PD-L1 expression in macrophages and their polarization | ||
Cancer cell derived EVs | miR‐200a | PD-L1 | Promote phosphorylation of PI3K downstream products by inhibiting PTEN translation; Promote phosphorylation of STAT1 by inhibiting SOCS1 translation | ||||
Lymphoma | Cancer cell derived EVs | unknown | CD8 + T cells | CTLA4 | Promote CTLA4 expression with unknown mechanism | Transform effect CD8 + T cells into regulatory CD8 + T cells with active immunosuppressive function, secreting inhibitory cytokines IL10 and TGF-β | |
unknown | Chimeric antigen receptor modified CD8 + T cells | CTLA4 | Promote CTLA4 expression with unknown mechanism | Damage tumor killing ability of chimeric antigen receptor modified CD8 + T cells | |||
Hepatocellular Carcinoma | Hepatic stellate cell derived EVs | circWDR25 | hepatic stellate cell | CTLA4 | Up-regulates ALOX15 via sponging mir-4474-3p, thereby promote CTLA4 expression | Facilitated HCC cell proliferation and invasion | |
Triple-negative Breast Cancer | Cancer cell derived EVs | CCL5 | M2-polarized tumor-associated macrophages | CTLA4 | Promote CTLA4 expression with unknown mechanism | Remodel the surrounding tumor stroma and immune infiltrate; increase tumor metastasis to the lung | |
Nasopharyngeal Carcinoma | Cancer cell derived EVs | Galectin-9 | Dendritic cells | TIM3 | Binding to TIM3 on the surface of dendritic cells induces the generation of regulatory dendritic cells. | Regulatory dendritic cells with mature phenotype inhibit T cell proliferation and secrete high level of IL-4. | |
Advanced Lung Cancer | Malignant pleural effusion derived EVs | CEACAM1 | CD3 + CD4-CD8-double-negative T cells | TIM3 | Binding to TIM3 on the surface of double-negative T cells downregulates their ability to kill tumors. | Create immunosuppressive environment for intrathoracic metastasis of tumors. | |
Epithelial Ovarian Cancer | Tumor-associated macrophages derived PD-L1+ exosomes | PD-L1 | CD8 + T cells | LAG3 | Unknow, possibly from the increased expression of CPT1A in CD8 + T cells that lead to an increase in reactive oxygen species-related cellular damage | Promote the apoptosis of CD8 + T cells | |
Lung Adenocarcinoma | Adipocyte‐derived exosomes | miR‐27a‐3p | CD4 + T cells | ICOS | Inhibit the transcription of ICOS | Reduce the release of IFN-γ by CD4 + T cells. |
