Table 2.

Soluble PD-L1 expression levels in different cancers and their correlation with disease prognosis and efficacy prediction.

Cancer type	Patients number	Treatment	Principal findings	Reference
NSCLC	233	Pembrolizumab or nivolumab	The disease control rate in the high sPD-L1 group was significantly lower than that in the low sPD-L1 group (37% vs. 57%, p = 0.0158); The high levels of serum sPD-L1 were independently associated with shorter PFS (HR 1.910; p = 0.061) and OS (HR 2.073; p = 0.034).	(83)
ESCC	153	/	sPD-L1 levels in patients with high PD-L1 expression levels in tumor tissue were significantly higher (p = 0.042); The OS of the sPD-L1-high group was significantly worse (p = 0.028).	(84)
OC	53	/	OC patients with a higher level of sPD-L1 in the peritoneal fluid had shorter 5-year survival than those with a lower sPD-L1 concentration (median 48 vs. 27 months).	(85)
Advanced rectal cancer	117	CRT	sPD-L1 levels were significantly increased after CRT. High sPD-L1 after CRT was associated with lymphovascular invasion and poorer DFS.	(80)
ESCC	190	Cytotoxic chemotherapy	Median OS of sPD-L1-high patients was lower than in patients with low sPD-L1 level (12 vs. 21 months, p < 0.001).	(86)
ccRCC	89	/	sPD-L1 was higher for metastatic patients compared to non-metastatic patients.	(87)
BC	132	/	Significantly higher serum sPD-L1 levels were found in patients with muscle invasive disease and metastatic disease (p < 0.05).	(88)
Urothelial Cancer	95	Chemotherapy or ICIs	High baseline sPD-L1 levels were associated with worse ECOG status (p = 0.007) and shorter OS for both chemotherapy- and ICI-treated patients (p = 0.002 and 0.040, respectively).	(89)
Glioma	60	RT	The baseline sPD-L1 levels were significantly associated with tumor grade, IDH-1 mutation status and Ki-67 expression; PFS and OS were significantly worse in patients with higher baseline levels of sPD-L1 (p = 0.027 and 0.008, respectively).	(90)
HCC	121	/	Patients with high sPD-L1 value (>96 pg/ml) had worse DFS and OS (HR 5.42, 95%CI (2.28-12.91), p < 0.001, and HR 9.67, 95%CI (4.33-21.59), p < 0.001).	(91)
STS	135	/	The high sPD-L1 (>44.26 pg/ml) group had significantly lower MS and lower OS than the low sPD-L1 group (≤44.26 pg/ml) at 5 years (42.4% vs. 88.4%, p < 0.001, and 64.1% vs. 89.2%, p = 0.011).	(92)
Melanoma	100	ICIs	Pretreatment levels of sPD-L1 were elevated in stage IV melanoma patient sera compared with healthy donors; High pretreatment levels of sPD-L1 were associated with increased likelihood of progressive disease in patients treated by ICIs; Elevated sPD-L1 after checkpoint blocker treatment was associated with PR.	(65)
Lung cancer	1188	ICIs	High sPD-L1 predicted worse OS (HR 1.60, 95%CI (1.31-1.96), p < 0.001) and lower ORR (odds ratio 0.52, 95%CI (0.35-0.80), p = 0.002) in patients treated with non-ICI therapies. High sPD-L1 was significantly associated with worse OS (HR 2.20, 95%CI (1.59-3.05), p < 0.001) and PFS (HR 2.42, 95%CI (1.72-3.42), p < 0.001) in patients treated with ICIs.	(93)

PD-L1, programmed death ligand 1; NSCLC, non-small cell lung cancer; PFS, progression-free survival; HR, hazard ratio; OS, overall survival; ESCC, esophageal squamous cell carcinoma; OC, ovarian cancer; CRT, chemoradiotherapy; DFS, disease-free survival; ccRCC, clear cell renal cell carcinoma; BC, bladder cancer; ICIs, immune checkpoint inhibitors; RT, radiotherapy; IDH-1, isocitrate dehydrogenase-1; HCC, hepatocellular carcinoma; CI, confidence interval; STS, soft tissue sarcoma; MS, metastasis-free survival; PR, partial response; ORR, objective response rate.