A pooled analysis of the prognostic value of PD-L1 in melanoma: evidence from 1062 patients.

Jing Yang,Li Jiang,Xiaoxiao Zuo,Yin Mi,Yifang Shui,Yue Zhang,Meilian Dong,Xiaobin Gu,Zhigang Zhang,Ke Liu,Yonggang Shi,Zheyan Liu

doi:10.1186/s12935-020-01187-x

Abstract

BackgroundProgrammed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). PD-1/PD-L1 interactions inhibit T cell-mediated immune responses, limit cytokine production, and promote tumor immune escape. Recently, many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. However, the results of these analyses remain a subject of debate. We have therefore carried out a meta-analysis to identify the prognostic role of PD-L1 in melanoma.MethodsA thorough medical literature search was performed in the databases PubMed, Web of Science, and Embase until October 2019. The pooled hazard ratios (HRs) and 95% confidence intervals (95% CIs) were calculated to evaluate the correlation between PD-L1 overexpression and prognosis. Publication bias was evaluated using Begg’s test and Egger’s test.ResultsThirteen articles with 1062 enrolled patients were included in this meta-analysis. High PD-L1 expression did not correlate with overall survival (OS) (HR = 0.93, 95% CI 0.57–1.52, P = 0.781) or progression-free survival (PFS) (HR = 0.82, 95% CI 0.43–1.54, P = 0.535). However, PD-L1 overexpression correlated with the absence of lymph node (LN) metastasis (OR = 0.46, 95% CI 0.22–0.95, P = 0.036). Further, there was no significant relationship between PD-L1 expression and sex (OR = 1.29, 95% CI 0.90–1.84, P = 0.159), age (OR = 0.90, 95% CI 0.51–1.57, P = 0.708), or Eastern Cooperative Oncology Group Performance Status (OR = 0.55, 95% CI 0.06–4.83, P = 0.592).ConclusionsThis meta-analysis suggested that PD-L1 expression did not predict an inferior prognosis in patients with melanoma. However, high PD-L1 expression was associated with absence of LN metastasis in such patients.

Highlights

Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1)
After careful reading of the full text, 41 studies were removed for the following reasons: 24 studies lacked necessary data, 4 studies did not apply the IHC method, 4 studies did not detect PD-L1 expression in tumor cells, 3 studies lacked survival data, 2 studies were non-human studies, 2 studies were letters or correspondences, 1 study was duplicated, and 1 study did not focus on PD-L1
There was no significant relationship between PD-L1 expression and sex (n = 7, Odds ratio (OR) = 1.29, 95% Confidence interval (CI) 0.90–1.84, P = 0.159), age (n = 4, OR = 0.90, 95% confidence intervals (95% CIs) 0.51– 1.57, P = 0.708), or ECOG Eastern Cooperative Oncology Group performance status (PS) (n = 2, OR = 0.55, 95% CI 0.06–4.83, P = 0.592, Table 3, Fig. 4)

Summary

Introduction

Programmed death-ligand 1 (PD-L1) was the first identified ligand of programmed death-1 (PD-1). Many studies have investigated the prognostic value of PD-L1 expression in patients with melanoma. We have carried out a metaanalysis to identify the prognostic role of PD-L1 in melanoma. The prognosis for patients with localized disease is promising, with a 5-year survival rate of over 90% [10]. Immune inhibitory signaling pathways have been recognized to play a pivotal role in the maintenance of an immunosuppressive microenvironment that favors cancer development [13]. In patients with melanoma, exosomal PD-L1 is an indicator of immune activation early after the initiation of treatment with immune checkpoint inhibitors (ICIs) and is associated with clinical response to ICIs [34]

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Conclusion