Clinical and Prognostic Value of Antigen-Presenting Cells with PD-L1/PD-L2 Expression in Ovarian Cancer Patients.

Anna Pawłowska,Agata Chudzik,Agnieszka Kwiatkowska,Bartłomiej Barczyński,Dorota Suszczyk,Rafał Tarkowski,Iwona Wertel,Jan Kotarski

doi:10.3390/ijms222111563

Anna Pawłowska, Agata Chudzik + Show 6 more

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https://doi.org/10.3390/ijms222111563

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Abstract

The latest literature demonstrates the predominant role of the programmed cell death axis (PD-1/PD-L1/PD-L2) in ovarian cancer (OC) pathogenesis. However, data concerning this issue is ambiguous. Our research aimed to evaluate the clinical importance of PD-L1/PD-L2 expression in OC environments. We evaluated the role of PD-L1/PD-L2 in OC patients (n = 53). The analysis was performed via flow cytometry on myeloid (mDCs) and plasmacytoid dendritic cells (pDCs) and monocytes/macrophages (MO/MA) in peripheral blood, peritoneal fluid (PF), and tumor tissue (TT). The data were correlated with clinicopathological characteristics and prognosis of OC patients. The concentration of soluble PD-L1 (sPD-L1) and PD-1 in the plasma and PF were determined by ELISA. We established an accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the tumor microenvironment. We showed an elevated level of sPD-L1 in the PF of OC patients in comparison to plasma and healthy subjects. sPD-L1 levels in PF showed a positive relationship with Ca125 concentration. Moreover, we established an association between higher sPD-L1 levels in PF and shorter survival of OC patients. An accumulation of PD-L1+/PD-L2+ mDCs, pDCs, and MA in the TT and high sPD-L1 levels in PF could represent the hallmark of immune regulation in OC patients.

Highlights

Ovarian cancer (OC) is mostly advanced during diagnosis, with widespread metastasis, and still has poor prognosis despite the new diagnostic and therapeutic approaches [1,2]
The highest percentage of myeloid (BDCA-1+CD19−) dendritic cells (DCs) was detected in the peritoneal fluid of the OC patients, and it was significantly higher than in peripheral blood (PB) (p < 0.0001; median 1.06% vs. 0.245%), and tumor tissue (p < 0.001; median 1.06% vs. 0.17%), than in PB of the control group (p < 0.0001; median 1.06% vs. 0.225% Figure 1A)
We showed differences in the distribution of myeloid and plasmacytoid DCs and MO/MA with PD-L1/PD-L2 expression in OC patients

Summary

Introduction

Ovarian cancer (OC) is mostly advanced during diagnosis, with widespread metastasis, and still has poor prognosis despite the new diagnostic and therapeutic approaches [1,2]. An outstanding role in the clinical outcome of patients with OC is played by the tumor microenvironment (TME). The studies prove that TME and T cell infiltration is strongly associated with the prognosis of ovarian cancer patients. The role of these structures is the regulation and maintenance of the balance between immune response and tolerance, including the inhibition of immune response targeted against host self-tissues. This is possible due to the enhancement and inhibition of the activity of T cells. One of the negative regulators of activated T cells is programmed cell death receptor 1 (PD-1) and its ligands (PD-L1, PD-L2) axis [4,8]

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