Prognostic value of tumor PD-L1 expression combined with CD8+ tumor infiltrating lymphocytes in high grade serous ovarian cancer

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Abstract

Expression of programmed cell death-ligand 1 (PD-L1) is known to be a mechanism whereby cancer can escape immune surveillance, but the relationship between tumor PD-L1 expression and tumor-infiltrating lymphocytes (TILs), and their association with clinical outcomes in patients with high grade serous ovarian cancer (HGSOC) remain ambiguous. We detected the expression of PD-L1 and CD3+, CD4+, CD8+ TILs in 107 patients with HGSOC by immunohistochemical analysis. Using a 5% threshold, 24.30% and 15.89% cases were found with positive expression of PD-L1 in the membrane of tumor cells and TILs respectively. Carcinoma PD-L1 expression mainly localized to the tumor invasive front and was associated with advanced FIGO stage (p = 0.023) and abundant stromal CD8+ TILs infiltration (p = 0.020). Tumors containing PD-L1+ TILs were more likely to have PD-L1 expression by the carcinoma cells (p < 0.001). Univariate and multivariate analyses demonstrated that a higher number of intraepithelial CD3+ or CD8+ TILs was an independent prognostic factor for longer overall survival (OS), whereas tumor PD-L1 expression was a predictive factor for poorer OS only in univariate analysis. PD-L1 expression in TILs was not a prognostic factor in univariate analysis. The Kaplan-Meier curves of the four sub-groups and log-rank test showed that patients with negative tumor PD-L1 expression/higher numbers of intraepithelial CD8+ TILs had the longest median OS, while those with positive tumor PD-L1 expression/lower numbers of intraepithelial CD8+ TILs had the shortest median OS (p < 0.001). Our results indicate that tumor PD-L1 expression in combination with intraepithelial CD8+ TILs infiltration has prognostic impact in patients with HGSOC. These biomarkers may be useful for the stratification of patients. Further evaluation of PD-1/PD-L1 as therapeutic targets for HGSOC is warranted.

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