Impact of PD-L1 and T-cell inflamed gene expression profile on survival in advanced ovarian cancer. Issue 7 (11th June 2020)

• Record Type: Journal Article
• Authors: Høgdall, Estrid; Høgdall, Claus; Vo, Thao; Zhou, Wei; Huang, Lingkang; Marton, Matthew; Keefe, Stephen M; Busch-Sørensen, Michael; Sørensen, Sarah M.; Georgsen, Jeanette; Mejlgaard, Else; Nedergaard, Lotte; Steiniche, Torben
• Is Part Of: International journal of gynecological cancer. Volume 30:Issue 7(2020)
• Page Start: 1034
• Page End: 1042
• Publication Date: 2020-06-11
• Subjects: medical oncology; Generative organs, Female -- Cancer -- Periodicals; 616.99465
• DOI: 10.1136/ijgc-2019-001109
• Languages: English
• ISSNs: 1048-891X

Abstract

Abstract : Objective: Programmed death ligand 1 (PD-L1) expression affects tumor evasion of immune surveillance. The prognostic value and relationship of PD-L1 expression to T-cell–inflamed immune signatures in ovarian cancer are unclear. The purpose of this study is to evaluate the impact of PD-L1 on overall survival and its correlation with an immune-mediated gene expression profile in patients with advanced ovarian cancer. Methods: PD-L1 expression in tumor and immune cells was assessed by immunohistochemistry, and PD-L1–positive expression was defined as a combined positive score ≥1; a T-cell–inflamed gene expression profile containing interferon γ response genes was evaluated using extracted RNA from surgical samples. Associations between PD-L1 expression, gene expression profile status, and overall survival were analyzed using the Kaplan-Meier method, log-rank test, and multivariate Cox proportional hazards regression models. Results: A total of 376 patients with advanced epithelial ovarian, primary peritoneal, or fallopian tube cancer treated by cytoreductive surgery and platinum-based therapy were included. PD-L1–positive expression was observed in 50.5% of patients and associated with more advanced stage (p=0.047), more aggressive histologic subtype (p=0.001), and platinum sensitivity defined by increasing treatment-free interval from first platinum-based chemotherapy to next systemic treatment (p=0.027). PD-L1–positive expression was associated with longer overall survival in multivariate analyses (adjusted HR 0.72, 95% CI 0.56 to 0.93). In subgroup analyses, this association was most pronounced in patients with partially platinum-sensitive disease (treatment-free interval ≥6 to <12 months). T-cell–inflamed gene expression profile status correlated with PD-L1 expression (Spearman, ρ =0.712) but was not an independent predictor of overall survival. Conclusion: PD-L1 expression is associated with longer overall survival among advanced ovarian cancer patients. PD-L1 expression may be an independent prognostic biomarker.