Increased Soluble PD-L1 Levels in the Plasma of Patients with Epithelial Ovarian Cancer Correlate with Plasma Levels of miR34a and miR200

Abstract

Recently, programmed cell death protein 1 (PD1) blocking and anti-programmed death-ligand 1 (PD-L1) agents were approved for the treatment of various human malignancies. Our study examined the expression of PD-L1 in neoplastic tissue (17 patients) and the plasma soluble (s)PD-L1 of 32 patients with ovarian carcinoma, in parallel with the levels of specific microRNAs (miRs), using immunohistochemistry, enzyme-linked immunosorbent assay (ELISA) and real-time quantitative reverse transcription polymerase chain reaction (qRT-PCR), respectively. PD-L1 levels were significantly higher in the plasma of patients with ovarian cancer compared to healthy women (p=0.01). High miR200 levels were related to high sPD-L1 levels (p=0.03), whilst high miR34a levels were associated with low sPD-L1 levels (p=0.02). Immunohistochemical expression of PD-L1 by cancer cells was not related to plasma miR levels, nor to the level of sPD-L1. As well as cancer cell expression of PD-L1, a high sPD-L1 level characterizes a subset of patients with ovarian cancer. The value of this latter feature as a biomarker for the administration of anti-PD-L1/PD1 therapy needs further evaluation. Micro-RNAs, such as miR34a and miR200, may have a role in the efficacy of immunotherapy.