Abstract
Background: Recently, blockade of immune checkpoint has emerged as one of the most potential treatments for solid tumors. Programmed cell death ligand 1(PD-L1), a member of the B7 family of molecules, plays a crucial role in tumor immunobiology. However, the prognostic significance of PD-L1 in cholangiocarcinoma (CCA) patients remains controversial. This study aimed to inquire into the prognostic and clinicopathological significance of PD-L1 in CCA via a meta-analysis.Methods: We searched PubMed, the Cochrane Library, Embase, Web of Science and Google Scholar up to April 2019, regardless of the region or language, for studies on the correlation between clinicopathology/prognosis and PD-L1 in patients with CCA. The pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated to investigate the prognostic significance of PD-L1 expression in cholangiocarcinoma. The odds ratios (ORs) were also determined to explore the association between PD-L1 expression and clinicopathological features.Results: Our meta-analysis included 11 studies with 1,066 patients. The meta-analysis of these studies indicated a trend that high PD-L1 expression indicated a poor OS, but the result was not statistically significant (HR = 1.62, 95% CI [0.98–2.68], p = 0.063). For DFS, although the pooled result is not statistically significant, it trends toward being significant that high PD-L1 expression indicated improved DFS (HR = 0.80, 95% CI [0.62, 1.04], p = 0.092). In subgroup analyses, the results were not consistent across the subgroups that were divided based on the publication year (before 2018: HR = 1.92, 95% CI [1.34–2.75], p < 0.001; after 2018: HR = 1.42, 95% CI [0.70–2.89], p = 0.335). Moreover, PD-L1 expression in TCs significantly correlated with the AJCC TNM stage of CCA (OR = 0.52, 95% CI [0.27, 0.99], p = 0.09).Conclusion: Our meta-analyses revealed that PD-L1 expressed in TCs was significantly correlated with the AJCC TNM stage of CCA. Based on the included studies, we found that PD-L1 indeed expressed in both TCs and ICs in CCA patients, raising the possibility of the use of anti-PD-1/PD-L1 therapy for CCA patients. In contrast, expression of PD-L1 did not seem to be associated with patient outcome in our study. The prognostic role of PD-L1 in CCA demands further investigation.
Highlights
Cholangiocarcinoma (CCA) is one of the most common and aggressive malignant tumors that arises from bile duct epithelial cells
The pooled result is not statistically significant, it trends toward being significant that high programmed cell death ligand 1 (PD-L1) expression indicated improved disease-free survival (DFS) (HR = 0.80, 95% CI [0.62, 1.04], p = 0.092) with moderate heterogeneity (I2 = 59.1%, p = 0.087) (Figure 3)
The results indicated that the significant correlation between PD-L1 expression in tumor cells (TCs) and overall survival (OS) became increasingly stable, starting with the study performed by Yu et al [31] (Figure 4A)
Summary
Cholangiocarcinoma (CCA) is one of the most common and aggressive malignant tumors that arises from bile duct epithelial cells. More and more studies have tried to investigate the interaction between the immune system and tumors. Tumors can escape immunosurveillance by expressing immune checkpoints [7]. The key role of the PD-L1/PD-1 axis, which is a major checkpoint pathway in tumor microenvironmental formation and immune escape, has been well established [8, 9]. As a member of the B7 family of molecules, PD-L1 expresses on the surface of tumor-associated antigenpresenting cells and malignant cells in numerous tumors that facilitates immune evasion via its interaction with PD-1 [14]. Whether PD-L1 has prognostic value in patients with CCA remains controversial. Blockade of immune checkpoint has emerged as one of the most potential treatments for solid tumors. The prognostic significance of PD-L1 in cholangiocarcinoma (CCA) patients remains controversial. This study aimed to inquire into the prognostic and clinicopathological significance of PD-L1 in CCA via a meta-analysis
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