The Programmed Death-1 Receptor, Programmed Death-1 Ligand (PD-1/PD-L1) and Apoptosis in Breast Cancer Patients: A potential Mechanism of Immune Escape

Document Type : Original Article

Authors

1 Faculty of Science, Elminia University, Egypt

2 Department of Cancer Management and Research, Medical Research Institute, Alexandria University, Alexandria, Egypt

3 Department of Pathology, Medical Research Institute, Alexandria University, Alexandria, Egypt

4 Department of Clinical Pathology, Faculty of medicine, Alexandria University, Alexandria, Egypt

5 Department of immunology and Allergy, Medical Research Institute, Alexandria University, Alexandria, Egypt

Abstract

Background: Interaction between programmed cell death ligand-1 (PD-L1) and its receptor PD-1 is a major inhibitory pathway in maintaining an immunosuppressive tumor microenvironment. The expression of PD-L1 in various solid tumors is proposed to function in preventing T-cell mediated tumor killing and activating tumor-suppressive cell populations through different mechanisms. B-cell Lymphoma-2 (Bcl-2) is a key anti-apoptotic protein that has been described as a mediator of cancer progression. The expression of PD-L1 on the activated T-cells supports their survival. Objectives:Evaluate the expression of PD-1, PD-L1 in relation to apoptosis among patients with breast cancer. PD-1, PD-L1 and Bcl-2 l were correlated with each other and with the clinicopathological features of the disease. Patients and Methods: This study was conducted on 55 breast cancer patients with different stages of the disease.20 healthy individuals were included as a control group. Patient groups were divided into an early and advanced-stage of the disease. The percentage of PD-1 and PDL-1 were measured in blood samples using flowcytometry. Quantitative detection of Bcl-2 protein was assessed using an enzyme linked immunosorbent assay. Results: PD-L1 expression was significantly associated with tumor grade, lymph node involvement, tumor size, vascular invasion and hormonal receptors. PD-1 positivity was significantly associated with lymph node involvement. A significant negative correlation was found between serum Bcl-2 and early-stage and lymph node involvement. However, a significant positive correlation existed between serum Bcl-2 and PD-L1+. Conclusions: The correlation between PD-L1+ expression and serum Bcl-2 concentration may highlight the role of apoptotic machinery in the pathogenesis of breast cancer.

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