Background: Strategies to improve the efficacy of the immune system against malignant tumors represent a major innovation focusing on the programmed cell death-1 receptor (PD-1), with its two ligands PD-L1 and PD-L2. The expression of PD-L1 has been evaluated in a number of different tumor types and can be used as a predictive biomarker for PD-1/PD-L1 checkpoint inhibitor treatment response. PD-L2 has not received as much attention and its role in modulating tumor immunity is less clear. We used a non-invasive, real-time liquid biopsy to better characterize PD-L1/-L2 expression on circulating epithelial tumor cells (CETCs) in breast cancer patients.

Methods: CETCs were determined from blood of 72 patients suffering from breast cancer. The number of vital CETCs and their expression of PD-L1 and PD-L2 were investigated using the maintrac® method.

Results: PD-L1 expressing CETCs were detected in 94.5 % of breast cancer patients whereas only 82% patients had PD-L2 positive CETCs. Breast cancer patients with metastatic disease had significantly more PD-L1 positive CETCs as compared to patients without metastasis (median 75% vs. 61.1%; p<0.05). The fraction of PD-L1 positive CETCs was significantly higher than the fraction of PD-L2 positive CETCs (54.6% vs. 28.7%; p<0.001). Moreover, we observed a significant heterogeneity in PD-L1 and PD-L2 immunostaining intensity across CETCs from the same patients.

Conclusion: Breast cancer patients have detectable CETCs with a high frequency of PD-L1 which correlates with progression of cancer disease. PD-L1 seems to be a major factor in immune evasion and may be a promising target of anticancer therapies. Monitoring the frequency of PD-L1 positive CETCs could reflect individual patient’s response to an anti-PD-1/PD-L1 therapy.

Citation Format: Monika Pizon, Dorothea Schott, Ulrich Pachmann, Katharina Pachmann. PD-L1 expression on circulating epithelial tumor cells (CETCs) correlates with the presence of metastasis in breast cancer patients and differs from PD-L2 expression [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2017; 2017 Apr 1-5; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2017;77(13 Suppl):Abstract nr 4955. doi:10.1158/1538-7445.AM2017-4955