Circulating sPD-L1 as a tumor microenvironment-derived biomarker: enhancing diagnostic discrimination accuracy in
Yue Zhang1, Shuyi Chen2, Jie Ma3
1Clinical Medical Laboratory Center, Gaogang Branch, Taizhou School of Clinical Medicine, Nanjing Medical University, The Affiliated Taizhou People's Hospital of Nanjing Medical University, Taizhou, 225300, China. yue_zhang@aa.seu.edu.cn.
Abstract:
Programmed cell death ligand 1 (PD-L1) plays a pivotal role in breast cancer immune evasion, yet tissue-based detection suffers from invasiveness and spatial heterogeneity. This study investigated circulating soluble PD-L1 (sPD-L1) as a non-invasive alternative for tumor microenvironment (TME) assessment and breast cancer diagnosis. Serum sPD-L1 levels were evaluated in healthy and breast-affected populations, with correlations assessed against inflammatory markers and clinicopathological parameters. Diagnostic performance of sPD-L1 was compared to conventional biomarkers using receiver operating characteristic (ROC) curve analysis. Cellular-level interactions were investigated by quantifying sPD-L1 and interleukin-6 (IL-6) in culture supernatants. Circulating sPD-L1 expression was significantly elevated in breast cancer versus healthy controls and benign cases, with notably higher levels observed in advanced stages and distant-metastatic cases. Moderate correlations were observed between serum sPD-L1 and various inflammatory indicators. Specifically, ROC curve analysis identified an optimal diagnostic cut-off value of 1.144 ng/mL for sPD-L1, with its discriminative power outperforming conventional biomarkers such as CEA and CA15-3. In vitro, peripheral blood mononuclear cells (PBMCs) co-cultured with breast cancer cells showed enhanced sPD-L1 and IL-6 secretion versus normal epithelial cell co-cultures, with parallel sPD-L1/IL-6 elevation. This coordinated induction was clinically validated by a positive serum sPD-L1/IL-6 correlation. In conclusion, circulating sPD-L1 represents a promising non-invasive biomarker reflecting TME and disease progression, supporting its potential utility for breast cancer diagnostic discrimination.
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