The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative breast cancers is associated with a favorable outcome of disease
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Gero Brockhoff1, Stephan Seitz1, Florian Weber2, Florian Zeman3, Monika Klinkhammer-Schalke4, Olaf Ortmann1 and Anja Kathrin Wege1
1Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany
2Institute of Pathology, University Hospital Regensburg, Regensburg, Germany
3Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany
4Tumor Center Regensburg, University of Regensburg, Regensburg, Germany
Gero Brockhoff, email: [email protected]
Keywords: triple negative breast cancer (TNBC); PD-(L)1
Received: November 30, 2017 Accepted: December 03, 2017 Published: December 27, 2017
Triple negative breast cancer patients have a poor course of disease not least because of limited treatment options however immunotherapy by targeting the PD-1/PD-L1 checkpoint system is a promising strategy to improve the outcome. Here we systematically investigated the expression of PD-1 on tumor infiltrating lymphocytes and PD-L1 on both tumor and infiltrated immune cells. Moreover, the PD-L1 gene status in tumor cells was assessed.
103 tissue microarray samples derived from triple negative breast cancer specimens were immunohistochemically stained against PD-1 and PD-L1. Dual marker fluorescence in-situ hybridization was applied to the PD-L1 gene and centromere region of chromosome 9. The disease free and overall survival rates were determined as a function of the PD-1/PD-L1 status.
A slight gain of the PD-L1 gene region was found in 55% of all samples but an elevated PD-L1/cen9 ratio was rather rare (7%). An increased gene dose is not associated with an enhanced protein expression and the PD-L1 expression only weakly correlates with the amount of immune cell infiltration. Instead, we found an association of PD-L1 expression on tumor and immune cells, respectively. Notably, the PD-1 expression on immune cells is associated with a favorable disease free and overall survival. PD-1 expression indicates an enhanced immunological anti-tumor activity and represents a favorable prognostic impact. A deeper understanding of factors that affect the regulation and function of the PD-1/PD-L1 system is required to establish predictive variables and to utilize the system for therapeutic intervention of triple negative breast cancer patients.
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