Abstract

This work investigated the clinical prognostic implications and biological function of plasma soluble programmed cell death ligand 1 in breast cancer patients. Plasma sPD-L1 levels of recurrent/metastatic breast cancer patients were determined, and the association of sPD-L1 levels and metastatic progression-free survival and metastatic overall survival was assessed. The PD-L1 expression on breast cancer cells was analyzed by flow cytometry, and the level of sPD-L1 in the supernatant of breast cancer cells was determined by enzyme-linked immunosorbent assay. Furthermore, the effect of sPD-L1 on the proliferation and apoptosis of T lymphocytes was detected by WST-1 assay and flow cytometry. The plasma sPD-L1 levels in 208 patients with recurrent/metastatic breast cancer before receiving first-line rescue therapy were measured. The optimal cutoff value of plasma sPD-L1 for predicting disease progression was 8.774 ng/ml. Univariate and multivariate analyses identified high sPD-L1 level (≥ 8.774 ng/ml) and visceral metastasis were independent factors associated with poor prognosis. Relevance analysis showed that the plasma sPD-L1 level was weaklyassociated with some systemic inflammation markers, including white cell count (WBC), absolute monocytecount, and absolute neutrophil count. Furthermore, we found sPD-L1 could be found in supernatant of culture with breast cancer cell line expressing PD-L1 on the cell surface and inhibit T lymphocyte function, playing a negative regulatory role in cellular immunity. sPD-L1 was a good tumor predictive maker in breast cancer and it may play a potentially important role in immune tolerance.

Highlights

  • Breast cancer is the most common malignancy in women and is the top cause of cancer-related death [1]

  • We found that sPDL1 could promote apoptosis of activated T lymphocytes, whereas the effect could be reversed by the adding of antibody against programmed death ligand 1 (PD-L1)

  • Recent studies indicated that cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs) and regulatory T cells (Tregs) within the tumor microenvironment were involved in the process of breast cancer growth, invasion and metastasis [26,27,28]

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Summary

Introduction

Breast cancer is the most common malignancy in women and is the top cause of cancer-related death [1]. Breast cancer can be curable, but the treatment of recurrent or metastatic breast cancer remains controversial. Appropriate treatment and monitoring the treatment response during the treatment are of important prognostic significance for recurrent or metastatic breast cancer. Carcinoembryonic antigen (CEA) and breast cancer antigen (CA153) are the most widely used serum markers, which play an important role in the process of monitoring relapse or disease progression in breast cancer patients [2]. CEA and CA153 are the non-specific tumor markers, CA153 response paralleled disease in only approximately 50% of patients who receive anthracycline-based first-line treatment in prospective phrase of II and III trials [3]. There is a need to identify biomarkers in breast cancer

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