Table 1.
Summary of studies investigating extracellular vesicles (EVs) in therapy monitoring.
| Type of Cancer | Monitored Therapy | Bio-Fluid EV Isolation Technique | Read-Out/Method | Comment | Reference |
|---|---|---|---|---|---|
| Glioblastoma | Immune checkpoint therapy | Blood, cell culture supernatant UC | ELISA and ddPCR | Glioblastoma EVs blocked T cell activation and proliferation in response to T cell receptor stimulation. PD-L1 was expressed on the surface of glioblastoma-derived EVs with potential to directly bind to PD1 | [17] |
| Melanoma | Immune checkpoint therapy | Blood, cell culture supernatant UC | FACS and ELISA | metastatic melanoma releases a high level of EVs that carry PD-L1 on their surface. Interferon-γ (IFN-γ) up-regulates PD-L1 on these vesicles, which suppresses the function of CD8 T cells and facilitates tumor growth. | [18] |
| Head and neck squamous cell carcinoma | Chemotherapy radiation | Blood, cell culture supernatant SEC | FACS and microarrays | Disease recurrence was associated with increase of total exosome proteins, after ipilimumab therapy, total exosome protein and tumor-derived and/or T-cell derived exosomes levels decreased, CD3+ and CD3+ CD15s+ exosomes stabilized and CD3+ CTLA4+ exosomes declined. | [19] |
| Breast cancer | Neo-adjuvant chemotherapy | Blood PEG based | Levels of EVs and CTCs were analyzed | Increased EVs concentration pre chemotherapy was associated with therapy failure and elevated EV concentration post-chemotherapy was associated with a reduced three-year progression-free and overall survival. | [24] |
| Breast cancer | Chemotherapy | Blood, cell culture supernatant UC | Protein levels and in vivo study | Chemotherapy-elicited EVs were enriched in annexin A6 (ANXA6). | [28] |
| Breast cancer | Chemotherapy | Cell culture supernatant, blood UC | miRNA | Chemotherapeutic agents induced breast cancer cells to secrete EV with the capacity to stimulate a cancer stem-like cell phenotype, promoting resistance to therapy | [29] |
| Breast cancer | Chemotherapy | Tissue and blood UC | mRNA and protein level | Breast cancer resistance protein was found to be upregulated at the mRNA and protein levels in circulating EVs from cancer patients that had a poor response to chemotherapy | [30] |
| Breast cancer | Immunotherapy | Cell culture supernatant UC | Protein level | Cetuximab treatment altered the protein content of EVs. | [33] |
| Glioblastoma | Surgical resection | Cell culture supernatant UC | mRNA and miRNA | serum (microvesicles) contain messenger RNA mutant/variants and microRNAs characteristic to patients with glioblastomas | [34] |
| Glioblastoma | Surgical resection | Blood UC | Mass spectrometry | EVs concentration was higher in GBM compared with healthy Controls, brain metastases and extra-axial brain tumors. Significant drop in plasma concentration was measured after surgery | [35] |
| Prostate cancer | Radiotherapy | Blood PEG based | miRNA PCR | higher vesicle concentration of exosomes and upregulation of hsa-let-7a-5p and hsa-miR-21-5p indicating radiation specific induction | [36] |
| Prostate cancer | Radiotherapy | Blood PEG based | miRNA next-generation sequencing | miR-654-3p and miR-379-5p expression after radiotherapy was associated with therapy response | [37] |
| Prostate cancer | Antiandrogen therapy | Cell culture supernatant UC | proteomics | vesicular protein cargo (ATP2B1/PMCA ATPase) possibly mediates resistance towards hormone therapy | [38] |
| Colorectal carcinoma | Surgical resection | Blood centrifugation of MPs | FACS from taMPs | EpCAM+ taMPs decreased 7 days after curative R0 tumour resection suggesting therapy succes | [39] |
| Liver cancer | Surgical resection | Blood centrifugation of MPs | FACS from taMPs | taMPs positive for AnnexinV, EpCAM and ASGPR1 decreased 7 days after curative R0 tumour resection | [40] |
| Colorectal carcinoma | Surgical resection | Blood UC | miRNA | low levels of vesicular miR-200c and miR-141 were associated with longer OS after CRC resection | [41] |
| Colorectal carcinoma | Radiotherapy | Blood CellSearch Imaging Flow Cytometry, Menarini® | relative changes in total number of CTCs, MPs, cell fragments | combination of relative changes in the total number of CTCs, MPs, and cell fragments together with perfusion CT scan classifies patients as responders or non-responders | [42] |
| Pancreatic cancer | Surgical resection | Blood UC | FACS | GPC1+ EVs significantly decreased after surgical resection, implacting therapy response | [43] |
| Pancreatic cancer | Neoadjuvant chemotherapy | Blood UC | exosomal DNA KRAS mutation ddPCR | vesicular KRAS mutation after neoadjuvant therapy is associated with disease progression and no option for surgical intervention; a reduction correlates with resectability | [44] |
| Lymphoma | Chemotherapy | Blood SEC | EV-associated extracellular RNA protein-bound miRNA | classical Hodgkin Lymphoma patients had enriched levels of miR24-3p, miR127-3p, miR21-5p, miR155-5p, and let7a-5p, follow-up of EV | [45] |
| Lymphoma | Chemotherapy | Blood | miRNA PCR | remission in diffuse large B cell Lymphoma was associated with increase of exosomal miR-451a; stable and progressive disease had no significant changes. miRNA revealed stable decrease in miRNA levels. | [46] |
CTC, circulating tumor cells; ddPCR, droplet digital PCR; EVs, extracellular vesicles; ELISA, enzyme-linked immunosorbent assay; FACS, fluorescent activated cell sorting; miRNA, microRNA; MPs, microparticles; PEG, polyethylene glycol; UC, ultracentrifuge; SEC, size exclusion chromatography; taMP, tumor-associated microparticles.