Correlation Between PD-L2 Expression and Clinical Outcome in Solid Cancer Patients: A Meta-Analysis

• Published in: Frontiers in oncology Vol. 9; p. 47
• Main Authors: Yang, Huayu, Zhou, Xiaoxiang, Sun, Lejia, Mao, Yilei
• Format: Journal Article
• Language: English
• Published: Switzerland Frontiers Media S.A 13-02-2019
• Subjects: immune checkpoint; meta-analysis; Oncology; PD-L2; prognostic biomarker; solid tumor; meta-analysis; solid tumor; PD-L2; prognostic biomarker; immune checkpoint
• ISSN: 2234-943X; 2234-943X
• DOI: 10.3389/fonc.2019.00047

Immune checkpoint inhibitors targeting the programmed cell death 1 (PD-1)/programmed cell death ligand 1 (PD-L1) pathway are a paradigm-shifting cancer therapy. Programmed cell death ligand 2 (PD-L2) is another ligand of PD-1, but its prognostic significance in solid cancer patients after surgery remains controversial. In this study, we aimed to reveal the prognostic implication of PD-L2 in solid tumors through a meta-analysis.
We searched PubMed, Embase and the Cochrane library for studies reporting the relationship between PD-L2 expression and prognosis or clinicopathological features in solid cancer patients after surgery from inception to January 2018, with language restricted to English. Pooled hazard ratios (HRs) and 95% confidence intervals (CIs) were determined to explore the prognostic value of PD-L2 expression. Odds ratios (ORs) were also calculated to investigate the relationship between PD-L2 expression and clinicopathological parameters.
Sixteen studies incorporating 3,533 patients were included in our meta-analysis. The pooled results revealed that PD-L2 overexpression was a weak negative predictor for overall survival (OS; HR = 1.38, 95% CI = 1.05-1.81,
= 0.021), as well as a strong predictor for poor disease-free survival (DFS)/progression-free survival (PFS) (HR = 1.44, 95% CI = 1.15-1.81,
= 0.001). In subgroup analyses, high PD-L2 expression revealed an unfavorable prognostic prediction for OS in hepatocellular carcinoma (HCC) (HR = 1.60, 95% CI = 1.12-2.29,
= 0.011) and for DFS/PFS in HCC (HR = 1.50, 95%CI = 1.04-2.16,
= 0.031) as well as clear cell renal cell carcinoma (HR = 1.45, 95% CI = 1.03-2.03,
= 0.033). Moreover, PD-L2 expression implied a weak trend toward the presence of lymphatic metastasis (presence vs. absence, OR = 1.61, 95% CI = 0.98-2.65,
= 0.061).
High PD-L2 expression may promote tumor metastasis and predict unfavorable prognosis in solid cancer patients after surgery, especially in HCC.