Research Papers:

Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent

Anke E.M. van Erp, Yvonne M.H. Versleijen-Jonkers _, Melissa H.S. Hillebrandt-Roeffen, Laurens van Houdt, Mark A.J. Gorris, Laura S. van Dam, Thomas Mentzel, Marije E. Weidema, C. Dilara Savci-Heijink, Ingrid M.E. Desar, Hans H.M. Merks, Max M. van Noesel, Janet Shipley, Winette T.A. van der Graaf, Uta E. Flucke and Friederike A.G. Meyer-Wentrup

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Oncotarget. 2017; 8:71371-71384. https://doi.org/10.18632/oncotarget.19071

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Anke E.M. van Erp1, Yvonne M.H. Versleijen-Jonkers1, Melissa H.S. Hillebrandt-Roeffen1, Laurens van Houdt1, Mark A.J. Gorris2, Laura S. van Dam3, Thomas Mentzel4, Marije E. Weidema1, C. Dilara Savci-Heijink5, Ingrid M.E. Desar1, Hans H.M. Merks6, Max M. van Noesel3, Janet Shipley7, Winette T.A. van der Graaf8, Uta E. Flucke9 and Friederike A.G. Meyer-Wentrup3

1Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands

2Department of Tumor Immunology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands

3Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands

4Dermatopathology Bodensee, Friedrichshafen, Germany

5Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands

6Department of Pediatric Oncology, Emma Children’s Hospital-Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands

7Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom

8The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom

9Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands

Correspondence to:

Yvonne M.H. Versleijen-Jonkers, email: [email protected]

Keywords: sarcoma, desmoplastic small round cell tumor (DSRCT), programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1), immune checkpoint blockade

Received: December 06, 2016     Accepted: June 27, 2017     Published: July 07, 2017


In order to explore the potential of immune checkpoint blockade in sarcoma, we investigated expression and clinical relevance of programmed cell death-1 (PD-1), programmed death ligand-1 (PD-L1) and CD8 in tumors of 208 sarcoma patients. Primary untreated osteosarcoma (n = 46), Ewing sarcoma (n = 32), alveolar rhabdomyosarcoma (n = 20), embryonal rhabdomyosarcoma (n = 77), synovial sarcoma (n = 22) and desmoplastic small round cell tumors (DSRCT) (n = 11) were examined immunohistochemically. PD-L1 expression was predominantly detected in alveolar and embryonal rhabdomyosarcomas (15% and 16%, respectively). In the alveolar subtype PD-L1 expression was associated with better overall, event-free and metastases-free survival. PD-1 expression on lymphocytes was predominantly seen in synovial sarcomas (18%). High levels of CD8+ lymphocytes were predominantly detected in osteosarcomas (35%) and associated with worse event-free survival in synovial sarcomas. Ewing sarcoma and DSRCTs showed PD-1 on tumor cells instead of on tumor infiltrating lymphocytes. Overall, expression and clinical associations were found to be subtype dependent. For the first time PD-1 expression on Ewing sarcoma (19%) and DSRCT (82%) tumor cells was described.

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