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. 2021 Mar 18;11(1):6400.
doi: 10.1038/s41598-021-85966-0.

PD-1 and PD-L1 expression on TILs in peritoneal metastases compared to ovarian tumor tissues and its associations with clinical outcome

Christine Bekos  1 , Dietmar Pils  2 , Sabine Dekan  3 , Gerda Hofstetter  3 , Peter Horak  4 , Alexander Reinthaller  1 , Stephan Polterauer  1 , Richard Schwameis  1 , Stefanie Aust  5
Affiliations

PD-1 and PD-L1 expression on TILs in peritoneal metastases compared to ovarian tumor tissues and its associations with clinical outcome

Christine Bekos et al. Sci Rep. .

Abstract

The therapeutic potential of immune checkpoint inhibitors is currently being investigated in epithelial ovarian cancer (EOC), but immunological effects of the programmed cell death protein 1 (PD-1)/programmed cell death 1 ligand 1 (PD-L1) axis in EOC still remain poorly understood. The aim of this study was thus to compare infiltration rates of PD-1 and PD-L1 expressing tumor infiltrating leucocytes (TILs) in primary ovarian tumor tissue and metastatic intraperitoneal implants and to investigate its impact on overall survival (OS). Tumor specimens (ovarian tumor tissues and intraperitoneal metastases) of 111 patients were used to investigate the PD-1, PD-L1 and CD8 expression rates on TILs and PD-L1 expression rate of tumor cells. The percentages of CD8, PD-1, and PD-L1 expressing subpopulations of TILs differ in primary ovarian tumor tissues and metastatic intraperitoneal implants. High PD-1 among TILs in peritoneal metastases were associated with favorable OS. High PD-L1 expression in TILs was associated with poor OS. Combining both factors in peritoneal metastases revealed an unfavorable prognosis. Primary ovarian tumor tissue and intraperitoneal metastatic tissues in EOC might have different strategies to evade immune control. Those findings are of importance for the process of biomarker assessment to predict patients' response to immunotherapy.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
Correlation of CD8 TILs (A), PD-1 TILs (B), PD-L1 TILs (C) and PD-L1 Tumor (D) in ovarian tumor tissue with the respective values in peritoneal metastases. °p < 0.1; ***p < 0.001. The top left and bottom right quadrants show histograms of the distribution of percentages. X-axis for the left quadrants is shown at the bottom and for the right side at the top of each panel. For Plots (B), (C), and (D) values were shown around the categorized percentages to see all patients.
Figure2
Figure2
(A) Representative immunohistochemistry (IHC) of CD8 in high grade serous ovarian cancer, 40×: CD8 positive tumor infiltrating lymphocytes (TILs) (B) IHC of PD-L1, 40×: PD-L1 positive TILs. (C) IHC of PD-L1, 40×: tumor cells stain positively for PD-L1, membrane staining was observed. (D) IHC of PD-1, 40×: PD-1 positive TILs.
Figure 3
Figure 3
Kaplan–Meier estimates for the clinicopathologic parameters histology (A), FIGO stage (B), and residual tumor mass after debulking surgery (C) and optimally dichotomized CD8 positive TILs in ovarian tumors (D), optimally dichotomized PD1 positive TILs (E) and optimally dichotomized PDL1 positive TILs in peritoneal metastases (F). P-values according to Log-Rank tests.
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