Research Papers:

Sensitive detection of PD-L1 expression on circulating epithelial tumor cells (CETCs) could be a potential biomarker to select patients for treatment with PD-1/PD-L1 inhibitors in early and metastatic solid tumors

Dorothea Sonja Schott _, Monika Pizon, Ulrich Pachmann and Katharina Pachmann

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Oncotarget. 2017; 8:72755-72772. https://doi.org/10.18632/oncotarget.20346

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Dorothea Sonja Schott1, Monika Pizon1, Ulrich Pachmann1 and Katharina Pachmann1

1Transfusion Center Bayreuth, Bayreuth, Germany

Correspondence to:

Dorothea Sonja Schott, email: [email protected]

Keywords: circulating epithelial tumor cells, programmed cell death ligand 1, programmed cell death ligand 2, checkpoint inhibitors

Received: November 24, 2016    Accepted: July 11, 2017    Published: August 18, 2017


Background: The current cancer research strongly focuses on immune therapies, where the PD-1, with its ligands plays an important role. It is known that PD-L1 is frequently up-regulated in a number of different cancers and the relevance of this pathway has been extensively studied and therapeutic approaches targeting PD-1 and PD-L1 have been developed. We used a non-invasive, real-time biopsy for determining PD-L1 and PD-L2 expression in CETCs of solid cancer patients.

Methods: CETCs were determined from blood of 128 patients suffering from breast (72), prostate (27), colorectal (18) and lung (11) cancer. The number of vital CETCs and the 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, 100% of prostate, 95.4% of colorectal and 82% of lung cancer patients whereas only 75% of breast cancer patients had PD-L2 positive CETCs. In the PD-L1 and PD-L2 expressing patients the cell fraction of PD-L1 positive CETCs is significantly higher than the fraction of PD-L2 positive CETCs (54.6% vs. 28.7%; p<0.001). 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).

Conclusion: PD-L1 seems to be a major factor in immune evasion and is highly expressed on CETCs regardless of the type of cancer. Monitoring the frequency of PD-L1 positive CETCs could reflect individual patient’s response for an anti-PD-1/PD-L1 therapy and may be a promising target of anticancer treatment.

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