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The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer

Muenst, S. ; Soysal, S. ; Gao, F. ; Obermann, E. ; Oertli, D. ; Gillanders, W.

In: Breast Cancer Research and Treatment, 2013, vol. 139, no. 3, p. 667-676

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    Titre
    • The presence of programmed death 1 (PD-1)-positive tumor-infiltrating lymphocytes is associated with poor prognosis in human breast cancer
    Auteur
    • Muenst, S.. Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland
    • Soysal, S.. Department of Surgery, Washington University School of Medicine, St. Louis, USA
    • Gao, F.. Division of Biostatistics, Washington University School of Medicine, St. Louis, USA
    • Obermann, E.. Institute of Pathology, University Hospital Basel, Schönbeinstrasse 40, 4031, Basel, Switzerland
    • Oertli, D.. Department of Surgery, University Hospital Basel, Basel, Switzerland
    • Gillanders, W.. Department of Surgery, Washington University School of Medicine, St. Louis, USA
    Type de document
    • Postprint
    Langue
    • Anglais
    Publié dans
    • Breast Cancer Research and Treatment, 2013, vol. 139, no. 3, p. 667-676. Springer US; http://www.springer-ny.com
    Autre version électronique
    Identifiant OAI-PMH
    • oai:doc.rero.ch:319935
    Summary
    Programmed death 1 (PD-1) is a co-inhibitory receptor in the CD28/CTL-4 family, and functions as a negative regulator of the immune system. Tumor-infiltrating lymphocytes (TIL) in many epithelial cancers express PD-1, suggesting that antitumor immunity may be modulated by the PD-1/PD-L1 signaling pathway, and promising results from two recent clinical trials with monoclonal antibodies targeting PD-1 or PD-L1 confirm the clinical relevance of this pathway in human cancer. To explore the role of PD-1+ TIL in human breast cancer, we performed immunohistochemistry studies on a tissue microarray encompassing 660 breast cancer cases with detailed clinical annotation and outcomes data. PD-1+ TIL were present in 104 (15.8%) of the 660 breast cancer cases. Their presence was associated with tumor size, grade, and lymph node status, and was differentially associated with the intrinsic subtypes of breast cancer. In univariate survival analyses, the presence of PD-1+ TIL was associated with a significantly worse overall survival (HR=2.736, p<0.001). In subset analyses, the presence of PD-1+ TIL was associated with significantly worse overall survival in the luminal B HER2− subtype (HR=2.678, p<0.001), the luminal B HER2+ subtype (HR=3.689, p<0.001), and the basal-like subtype (HR=3.140, p<0.001). This is the first study to demonstrate that the presence of PD-1+ TIL is associated with poor prognosis in human breast cancer, with important implications for the potential application of antibody therapies targeting the PD-1/PD-L1 signaling pathway in this disease