Table 2.
sEV PD-L1 as a diagnostic and prognostic biomarker in cancer.
| Cancer type | Sample type | Detection method of sEV PD-L1 | Number of cases | Relationship between sEV PD-L1 and clinical features | Relationship between sEV PD-L1 and pathological features | Diagnostic and/or prognostic significance | References |
|---|---|---|---|---|---|---|---|
| Lung cancer | Serum | ELISA | 85 (Stage I–IV) | The level of sEV PD-L1 in III/IV NSCLC patients was significantly higher than that of I/II NSCLC patients; the level of circulating sEV PD-L1 was positively correlated with tumor size | The level of circulating sEV PD-L1 was positively correlated with lymph node metastasis and distant metastasis | The feasibility of sEV PD-L1 to be used as a diagnostic biomarker for screening of early and late NSCLC patients needs to be further validated | 35 |
| Compact surface plasmon resonance (SPR) biosensor and ELISA | 5 | The level of sEV PD-L1 in NSCLC patients was higher than that in HD | ND | 24 | |||
| Surface-Enhanced Raman Scattering (SERS) immunoassay | 17 (Stage I–IV) | The level of sEV PD-L1 in early (stage I-II) and late (stage III-IV) NSCLC patients was significantly higher than that in HD (n = 12) | 22 | ||||
| Immunobiochip | 20 (Stage I–IV) | miR-21 and thyroid transcription factor-1 (TTF-1) mRNA in PD-L1-positive sEVs can distinguish HD from early and late NSCLC patients more sensitively and specifically than miR-21 and TTF-1 mRNA in whole serum | 25 | ||||
| Head and neck squamous cell carcinoma | Plasma | Flow cytometry | 40 (Stage I–IV) | The percentage and relative fluorescence value (RFVs) of PD-L1-positive sEVs in AD (n = 23) patients was significantly higher than that in NED (n = 17) patients; the percentage and RFVs of PD-L1-positive sEVs in late (stage III-IV) patients (n = 16) was significantly higher than that of early (stage I-II) patients (n = 24) | The percentage and RFVs of PD-L1-positive sEVs in patients with positive lymph nodes (n = 22) was significantly higher than that in patients with negative lymph nodes (n = 18) | sEV PD-L1 is potential to serve as biomarker for disease progression and clinical stage in HNSCC | 19 |
| Flow cytometry | 22 (Stage I–IV) | CD3+ sEV PD-L1 level, but not CD3− fractions, from patients with late (stage III-IV) NSCLC was significantly elevated versus early (stage I-II) NSCLC patients | CD3− sEV PD-L1 in patients with lymph node metastasis was significantly higher than patients with no lymph node metastasis | 38 | |||
| Gastric cancer | Serum | ELISA | 69 (Stage I–III) | Higher baseline level of circulating sEV PD-L1 was associated with lower overall survival in 31 metastatic gastric cancer patients receiving chemotherapy; the level of sEV PD-L1 was an independent prognostic factor in gastric cancer patients | ND | sEV PD-L1 is a promising biomarker for predictive prognosis and immunosuppression status in metastatic gastric cancer patients | 29 |
| Plasma | ELISA | 21 (Stage III–IV) | Circulating sEV PD-L1 increased more significantly after 5-fluorouracil (5-FU) treatment in clinical non-responders compared with the responders | 27 | |||
| Pancreatic cancer | Serum | Flow cytometry | 55 | The median postoperative survival time of sEV PD-L1-positive pancreatic cancer (17.2 months) were significantly longer than sEV PD-L1-negative patents (7.84 months) | ND | sEV PD-L1 can serve as a negative prognostic factor for pancreatic cancer | 20 |
| Glioma | Plasma | Western blotting | 19 | PD-L1 was highly expressed in circulating sEVs from both stage IV glioblastoma patients and HD, and the difference was not significant | ND | sEV PD-L1 is not a reliable predictor in glioblastoma diagnosis | 18 |
| Serum and plasma | Droplet PCR | 21 | The DNA level of sEV PD-L1 was positively correlated with the tumor volume (up to 60 mm3) and the level of PD-L1 in tumor tissue determined by IHC | Gene expression level of sEV PD-L1 is a potential marker in early diagnose of glioblastoma cancer | 17 | ||
| Plasma | qRT-PCR | 34 | Glioma patients’ response to vaccination therapy can be predictive by sEV PD-L1 mRNA level | 46 | |||
| Other | Plasma | HOLMES-ExoPD-L1/ELISA | 34 (15 Stage I–IV, urothelial carcinoma, 11 gastric adenocarcinoma, 6 prostate adenocarcinoma, 1 ovarian sarcoma, 1 SCLC) | The level of circulating sEV PD-L1 can effectively distinguish cancer patients from HD | sEV PD-L1 concentration was highly positively correlated with the metastasis | sEV PD-L1 is expected to be a predictor for disease progression in cancer | 23 |
AD active disease, NED no evidence of disease, HD healthy donors, ND not defined, SCLC small cell lung cancer, NSCLC non-small cell lung cancer, HNSCC head and neck squamous cell carcinoma.