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

Abstract

// Anke E.M. van Erp 1 , Yvonne M.H. Versleijen-Jonkers 1 , Melissa H.S. Hillebrandt-Roeffen 1 , Laurens van Houdt 1 , Mark A.J. Gorris 2 , Laura S. van Dam 3 , Thomas Mentzel 4 , Marije E. Weidema 1 , C. Dilara Savci-Heijink 5 , Ingrid M.E. Desar 1 , Hans H.M. Merks 6 , Max M. van Noesel 3 , Janet Shipley 7 , Winette T.A. van der Graaf 8 , Uta E. Flucke 9 and Friederike A.G. Meyer-Wentrup 3 1 Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands 2 Department of Tumor Immunology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands 3 Princess Máxima Center for Pediatric Oncology, Utrecht, The Netherlands 4 Dermatopathology Bodensee, Friedrichshafen, Germany 5 Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands 6 Department of Pediatric Oncology, Emma Children’s Hospital-Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands 7 Sarcoma Molecular Pathology Team, Divisions of Molecular Pathology and Cancer Therapeutics, Institute of Cancer Research, London, United Kingdom 8 The Institute of Cancer Research and The Royal Marsden NHS Foundation Trust, London, United Kingdom 9 Department of Pathology, Radboud University Medical Center, Nijmegen, The Netherlands Correspondence to: Yvonne M.H. Versleijen-Jonkers, email: Yvonne.Versleijen-Jonkers@radboudumc.nl 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 ABSTRACT 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.