Oncotarget

Research Papers:

Tumoral PD-L1 expression defines a subgroup of poor-prognosis vulvar carcinomas with non-viral etiology

Thomas Hecking, Thore Thiesler, Cynthia Schiller, Jean-Marc Lunkenheimer, Tiyasha H. Ayub, Andrea Rohr, Mateja Condic, Mignon-Denise Keyver-Paik, Rolf Fimmers, Jutta Kirfel, Walther Kuhn, Glen Kristiansen and Kirsten Kübler _

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Oncotarget. 2017; 8:92890-92903. https://doi.org/10.18632/oncotarget.21641

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Abstract

Thomas Hecking1,*, Thore Thiesler2,*, Cynthia Schiller2, Jean-Marc Lunkenheimer2,4, Tiyasha H. Ayub1, Andrea Rohr1,5, Mateja Condic1, Mignon-Denise Keyver-Paik1, Rolf Fimmers3, Jutta Kirfel2, Walther Kuhn1, Glen Kristiansen2,* and Kirsten Kübler1,6,7,8,*

1Department of Obstetrics and Gynecology, Center for Integrated Oncology, University of Bonn, Bonn, Germany

2Institute of Pathology, Center for Integrated Oncology, University of Bonn, Bonn, Germany

3Institute of Medical Biometry, Informatics and Epidemiology, Center for Integrated Oncology, University of Bonn, Bonn, Germany

4Hospital of Augustinian Nuns, Cologne, Germany

5Ärzte am Bärenplatz, Hornberg, Germany

6Broad Institute of MIT and Harvard, Cambridge, MA, USA

7Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA

8Harvard Medical School, Boston, MA, USA

*These authors have contributed equally to this work

Correspondence to:

Kirsten Kübler, email: [email protected]

Keywords: vulvar cancer, PD-L1, immune checkpoint, prognostic factor, HPV

Received: June 27, 2017     Accepted: August 25, 2017     Published: October 06, 2017

ABSTRACT

Vulvar cancer is rare but incidence rates are increasing due to an aging population and higher frequencies of young women being affected. In locally advanced, metastatic or recurrent disease prognosis is poor and new treatment modalities are needed. Immune checkpoint blockade of the PD-1/PD-L1 pathway is one of the most important advancements in cancer therapy in the last years. The clinical relevance of PD-L1 expression in vulvar cancer, however, has not been studied so far. We determined PD-L1 expression, numbers of CD3+ T cells, CD20+ B cells, CD68+ monocytes/macrophages, Foxp3+ regulatory T cells and CD163+ tumor-associated macrophages by immunohistochemistry in 103 patients. Correlation analysis with clinicopathological parameters was undertaken; the cause-specific outcome was modeled with competing risk analysis; multivariate Cox regression was used to determine independent predictors of survival. Membranous PD-L1 was expressed in a minority of tumors, defined by HPV-negativity. Its presence geographically correlated with immunocyte-rich regions of cancer islets and was an independent prognostic factor for poor outcome. Our data support the notion that vulvar cancer is an immunomodulatory tumor that harnesses the PD-1/PD-L1 pathway to induce tolerance. Accordingly, immunotherapeutic approaches might have the potential to improve outcome in patients with vulvar cancer and could complement conventional cancer treatment.


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