Table 2 EVs as Predictor of immune checkpoint inhibition therapy.
From: Influencing immunity: role of extracellular vesicles in tumor immune checkpoint dynamics
Clinical application | Target immune checkpoint | Cancer involved | Protocol | Sample quantity | Outcome measurement | Reference |
|---|---|---|---|---|---|---|
Monitoring the efficacy of immune checkpoint blocking therapy | PD-L1 | Lung Adenocarcinoma, Lung Squamous Carcinoma, Esophageal Carcinoma, Colorectal Carcinoma, Cholangiocarcinoma, Nasopharyngeal Carcinoma, Lung Small Cell Carcinoma, Lung Large Cell Carcinoma | Combine extracellular vesicles with other serum biomarkers to monitor the therapeutic effect of immune checkpoint therapy | 44 | Clinical response was determined as best response based on immune-related RECIST (irRECIST). Progression-free survival (PFS) was calculated from the time of treatment till progression or the last follow-up visit. | |
PD-L1 | Nonsmall Cell Lung Cancer | Quantification of EVs-PD-L1 levels in patient plasma through the ELISA. | 120 | The patient’s recurrence-free survival time. | ||
PD-L1/PD-1 | Nonsmall Cell Lung Cancer | Combine PD-1/PD-L1, NK immune checkpoint markers and cytokines derived from extracellular vesicles to monitor the therapeutic effect of immune checkpoint therapy | 17 | Tumor response detected on PET-CT 4-6 months after the initiation of treatment. | ||
PD-L1 | Melanoma | Collecting fecal samples from patients at various time points after the initiation of immunotherapy and measuring the levels of EVs-PD-L1 to assess its relationship with the patients’ treatment response. | 20 | Incidence and timing of immune-related adverse events; Assessment of immunotherapy response based on irRECIST; Progression-free survival of patients. | ||
PD-L1 | Nonsmall Cell Lung Cancer | Efficiently and high-purely isolate EVs using Tim4-functionalized magnetic core-shell metal-organic framework (Fe3O4@SiO2-ILI-01@Tim4) that contains a strongly hydrophilic organic ligand 1,3-bis(4-carboxybutyl) imidazolium bromide (ILI). Subsequently, EVs-PD-L1 levels are quantified through high-throughput immunofluorescence assay. | 14 | The difference in EVs-PD-L1 levels from tumor cell sources between cancer patients and healthy donors. | ||
PD-L1 | Nonsmall Cell Lung Cancer | By introducing a multi-component nucleotide enzyme linked to a fluorescent reporter protein, a significant amount of fluorescence signal is generated through the activation of the enzymatic cleavage of the fluorescent reporter protein under the simultaneous stimulation of the PD-L1 Aptamer and the Aptamer adhered to EVs’ lipid membrane through hydrophobic lipid affinity. | 21 | Differences in EVs-PD-L1 levels between patients with progressing tumors and patients without progression following ICB therapy. | ||
LAG3 | Lung Adenocarcinoma | Indirect monitoring of ICB treatment response by monitoring the levels of the LAG3 ligand FGL1 on plasma EVs | 17 | Differences in EVs-FGL1 levels among the disease progression group, disease control group, and disease remission group. | ||
TIM-3 | Hepatocellular Carcinoma | Indirectly monitoring ICB treatment response by monitoring the regulation of TIM3 expression in EVs-circUHRF1. | 30 | Assess immunotherapy response based on irRECIST and CT scanning. | ||
As a biomarker for cancer diagnosis | PD-L1 | Nonsmall Cell Lung Cancer | First, TiO2 magnetic nanoparticles were combined with exosome phospholipid hydrophilic phosphate heads to capture exosomes indiscriminately. Then the PD-L1 marker “Au@Ag@MBA” required for Surface-Enhanced Raman Scattering (SERS) immunoassay was added to accurately quantify EVs-PD-L1. | 29 | Differences in EVs-PD-L1 levels among patients with advanced non-small cell lung cancer, early stage cancer, and healthy candidates. | |
PD-L1 | Melanoma | developed a dual-target-specific aptamer recognition activated in situ connection system on exosome membrane combined with droplet digital PCR (ddPCR) for quantitation of tumor-derived exosomal PD-L1 (Exo-PD-L1). | 45 | The difference in EVs-PD-L1 levels from tumor cell sources between cancer patients and healthy donors. | ||
PD-L1 | Breast Cancer | Two sets of DNA molecular machines are designed to directly amplify the detection signals for ExoPD-L1 protein and ExomiR-21 microRNA in exosome lysates. | 16 | The relative expression levels of ExomiR-21 and ExoPD-L1 in the plasma exosomes. | ||
PD-L1 | Nonsmall Cell Lung Cancer | Conjugating the PD-L1 aptamer to ternary metal-metalloid palladium-copper-boron alloy microporous nanospheres capable of conducting electrical signals, to assess the level of EVs-PD-L1 based on its characteristic electrical signal. | 10 | The difference in EVs-PD-L1 levels from tumor cell sources between cancer patients and healthy donors. | ||
LAG3 | Lung Adenocarcinoma | Diagnosing lung adenocarcinoma patients by monitoring the levels of LAG3 ligand FGL1 on plasma EVs and assessing its relationship with tumor progression in patients. | 69 | The differences in EVs-FGL1 levels between healthy individuals and lung adenocarcinoma patients, as well as among patients at different clinical stages. |
