Researchers at Nanjing Medical University in China have identified significantly elevated levels of soluble PD-L1 (sPD-L1) in the serum of patients with breast cancer compared to healthy women or those with benign breast pathology. The concentration of this biomarker increased further in patients with advanced stages of the disease and those exhibiting distant metastasis, according to a study led by Xiaobin Zhou.
The diagnostic reliability of sPD-L1, using a selected threshold, surpassed that of commonly used tumor markers including carcinoembryonic antigen (CEA), CA15-3, and CA125. Zhou, a co-director of the study, noted that unlike these traditional markers, sPD-L1 demonstrates a balanced sensitivity, and specificity. However, the researchers found that combining sPD-L1 measurements with CEA and CA15-3 further improved diagnostic accuracy.
The study also revealed numerous correlations between sPD-L1 levels and inflammatory indices, as well as cellular biomarkers, suggesting a link between elevated sPD-L1 and a systemic immunosuppressive state. In vitro experiments demonstrated the immunomodulatory role of sPD-L1, showing that silencing the corresponding gene reduced the proliferation and migration of tumor cells.
Zhou emphasized the limitations of current PD-L1 assessment methods, which rely on tissue evaluation and require repeated biopsies due to tumor heterogeneity. “Tissue assessment of PD-L1 presents critical limitations, such as the need for repeated biopsies and tumor heterogeneity,” Zhou stated. The current findings align with previously reported associations between sPD-L1 and tumor progression in other cancer types, he added.
The research positions circulating sPD-L1 as a potentially valuable, minimally invasive biomarker for diagnosing breast cancer and evaluating the risk of progression and metastasis. A study published in 2022 in Frontiers in Immunology found that PD-L1 protein expression was associated with quality clinical outcomes in breast cancer patients receiving neoadjuvant chemotherapy. The study, conducted by researchers at Tongji Hospital and the National Cancer Center in China, utilized semiquantitative analysis of PD-L1 expression in tumor cells.
Another study, detailed in a publication from Campus Kinesico, highlighted the significance of PD-L1 expression in primary breast cancer. Researchers Neelima Vidula, Christina Yau, and Hope S. Rugo found that higher PD-1 expression was notably more prevalent in aggressive forms of breast cancer, particularly triple-negative breast cancer (TNBC) and HER2-positive breast cancer. The study also indicated that patients with the lowest quintile of PD-L1 expression experienced poorer recurrence-free survival, with a hazard ratio of 2.33, indicating more than double the risk of recurrence compared to patients with higher levels of PD-L1.
China has been rapidly developing its own domestic versions of PD-1/PD-L1 inhibitors, with over a dozen approved by the National Medical Products Administration (NMPA) as of December 2025, according to a report by MolecularCloud.org. These developments reflect China’s push for self-sufficiency in healthcare and could have implications for global access to cancer treatment.