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, Friederike A. G. Meyer-Wentrup

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72 Citations (Scopus)

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
Original languageEnglish
Pages (from-to)71371-71384
JournalOncotarget
Volume8
Issue number41
Early online date2017
DOIs
Publication statusPublished - 2017

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