The presence of PD-1 positive tumor infiltrating lymphocytes in triple negative breast cancers is associated with a favorable outcome of disease

// Gero Brockhoff 1 , Stephan Seitz 1 , Florian Weber 2 , Florian Zeman 3 , Monika Klinkhammer-Schalke 4 , Olaf Ortmann 1 and Anja Kathrin Wege 1 1 Department of Gynecology and Obstetrics, University Medical Center Regensburg, Regensburg, Germany 2 Institute of Pathology, University Hospital Regensburg, Regensburg, Germany 3 Center for Clinical Studies, University Hospital Regensburg, Regensburg, Germany 4 Tumor Center Regensburg, University of Regensburg, Regensburg, Germany Correspondence to: Gero Brockhoff, email: gero.brockhoff@ukr.de Keywords: triple negative breast cancer (TNBC); PD-(L)1 Received: November 30, 2017      Accepted: December 03, 2017      Published: December 27, 2017 ABSTRACT 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.