Prognostic significance of programmed cell death 1 (PD-1) or PD-1 ligand 1 (PD-L1) Expression in epithelial-originated cancer: a meta-analysis

Abstract

The expression of programmed cell death 1 (PD-1) and its ligand (PD-L1) has been observed in various epithelial-originated malignancies. However, whether the expression of PD-L1 on tumor cells or the expression of PD-1 on tumor-infiltrating lymphocytes (TILs) is associated with patients' survival remains controversial.Electronic databases were searched for eligible literatures. Data of hazard ratio (HR) for overall survival (OS) with 95% confidence interval (CI) according to the expression status of PD-L1 or PD-1 evaluated by immunohistochemistry were extracted. The outcomes were synthesized based on random-effects model. Subgroup analyses were proposed.Twenty-nine studies covering 12 types of epithelial-originated malignancies involving 7319 patients (2030/3641 cases for PD-L1 positive/negative, 505/1143 cases for PD-1 positive/negative) with available data of the outcome stratified by PD-L1/PD-1 status were enrolled. Epithelial-originated cancer patients with positive expression of PD-L1 on tumor tissues were associated with significantly poorer OS when compared to those with negative expression of PD-L1 (HR 1.81, 95% CI 1.33-2.46, P < 0.001). Similarly, patients with PD-1 positive expression on TILs had significantly shorter OS than the PD-1 negative group (HR 2.53, 95% CI 1.22-5.21, P = 0.012). In analyses of PD-L1, all subgroups showed consistent trends toward unfavorable prognoses of patients with positive PD-L1 expression, regardless of antibodies and evaluation cutoffs. Subgroup analyses on PD-1 were not available due to limited data.PD-L1 or PD-1 expression status is a significant prognostic factor in epithelial-originated malignancies.

FIGURE 1

Flow chart of study selection. CI = confidence interval, HR = hazard ratio, IHC = immunohistochemistry, OS = overall survival, PD-1 = programmed cell death 1, PD-L1 = PD-1 ligand 1.

FIGURE 2

Meta-analysis of PD-L1 positive versus PD-L1 negative on tumor tissues (A) PD-1 positive versus PD-1 negative on tumor infiltrating lymphocytes (B) of epithelial-originated cancer patients in terms of overall survival. CI = confidence interval, HR = hazard ratio, PD-1 = programmed cell death 1, PD-L1 = PD-1 ligand 1.

FIGURE 3

Subgroup analyses of PD-L1 positive versus PD-L1 negative on tumor tissues of epithelial-originated cancer patients in terms of overall survival (number of studies). CI = confidence interval, HR = hazard ratio, IHC = immunohistochemistry, PD-L1 = programmed cell death 1 ligand 1.