Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Hara Polioudaki; Anastasia Mala; Eleni Gkimprixi; Maria A Papadaki; Amanda Chantziou; Maria Tzardi; Dimitris Mavroudis; Sofia Agelaki; Panayiotis A Theodoropoulos

doi:10.3390/cancers12123735

Epithelial/Mesenchymal Characteristics and PD-L1 Co-Expression in CTCs of Metastatic Breast Cancer Patients Treated with Eribulin: Correlation with Clinical Outcome

Cancers (Basel). 2020 Dec 11;12(12):3735. doi: 10.3390/cancers12123735.

Authors

Affiliations

¹ Laboratory of Biochemistry, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece.
² Department of Medical Oncology, University General Hospital of Heraklion, 71110 Heraklion, Crete, Greece.
³ Laboratory of Translational Oncology, School of Medicine, University of Crete, 71003 Heraklion, Crete, Greece.
⁴ Department of Pathology, University General Hospital of Heraklion, 71110 Heraklion, Crete, Greece.

Abstract

We aimed to evaluate the co-expression of PD-L1 and epithelial-mesenchymal markers in CTCs from metastatic breast cancer (MBC) patients and to determine if there is any relationship with patients' outcome after eribulin treatment. Using cytospin preparations of peripheral blood mononuclear cells (PBMCs) from MBC patients treated with eribulin and a combination of immunocytochemistry and immunofluorescence, we quantified PD-L1, keratins and vimentin in single and cluster CTCs on days 1 and 8 of the first-treatment cycle. CTCs (n = 173) were found in 31 out of 38 patients. At baseline, the presence of cluster CTCs (p = 0.048), cluster mesenchymal CTCs (mCTCs) (p = 0.0003) or cluster PD-L1⁺mCTCs (p = 0.006) was associated with shorter overall survival (OS). In multivariate cox regression analysis, the detection of cluster mCTCs was the only parameter associated with increased risk of death (p = 0.024). On day 8 post-eribulin administration, PD-L1⁺mCTCs and especially single PD-L1⁺mCTCs decreased in 75% and 89% of patients, respectively. The detection of single PD-L1⁺mCTCs after eribulin treatment was correlated with shorter PFS (p = 0.047) and OS (p = 0.020). In conclusion, our study identified for the first time that cluster and single PD-L1⁺mCTCs subpopulations are of clinical significance in patients with MBC and highlighted the importance of CTC phenotyping during treatment with eribulin.

Keywords: CTCs; EMT status; MET; PD-L1; biomarkers; eribulin; immunocytochemistry combined to immunofluorescence; liquid biopsy; metastatic breast cancer.