Table 3.

Quantitation of exosomal PD-L1 and its clinical effects on PD-1 therapy.

Cancer type	How the studies were done	Quantitation of exosomal PD-L1 in patients	Clinical effects on PD-1 therapy	Clinical implications and significance	References
Metastatic melanoma	PD-L1 was high in exosomes from metastatic melanoma by WB. Exosome PD-L1 could bind to PD-1 on T cells by electron microscopy, ELISA and confocal microscopy analysis. To predict the efficacy of immunotherapy by detecting the pre-treatment level of PD-L1	0.1~5.4 ng/ml	Exosomal PD-L1 >2.43 was associated with a better response to anti-PD-1 therapy on ORR, PFS and OS	For providing a rationale for application of exosomal PD-L1 as a predictor for anti-PD-1 therapy in melanoma	(8)
HNSCC	Exosomes isolated by size exclusion chromatography were captured on CD63 beads. The correlation of percentages and mean fluorescence intensities of PD-L1+ exosome with the patients' clinicopathological data by FCM analysis	Approximately 25~83% of exosomal PD-L1/ml plasma in AD patients; 15~35% of exosomal PD-L1/ml plasma in NED patients	NA	To predict HNSCC patients' disease activity, the UICC stage and the lymph node status by levels of exosomal PD-L1	(11)
Melanoma	To investigate response of exosomal PD-L1 to nivolumab and pembrolizumab in patients with melanoma and NSCLC, blood was obtained at time point 0 and after 2 months	140~2,500 (copies/ml) 95~190 (copies/ml) 0~90 (copies/ml)	CR+PR SD PD	PD-L1 mRNA in exosomes is associated with response to anti-PD-1 in melanoma and NSCLC	(12)
NSCLC		330~1,700 (copies/ml) 380~530 (copies/ml) 0~650 (copies/ml)	PR SD PD		(12)

ORR, objective response rate; FCM, flow cytometry; PFS, progression free survival; OS, overall survival; HNSCC, head and neck squamous cell carcinoma; AD, active disease; NED, no evidence of disease; NA, not applicable; CR, complete response; PR, partial response; SD, stable disease; PD, progression of disease.