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

van Erp, A.E.M.; Versleijen-Jonkers, Y.M.H.; Hillebrandt-Roeffen, M.H.S.; van Houdt, L.; Gorris, M.A.J.; van Dam, L.S.; Mentzel, T.; Weidema, M.E.; Savci-Heijink, C.Dilara.; Desar, I.M.E.; Merks, H.H.M.; van Noesel, M.M.; Shipley, J.; van der Graaf, W.T.A.; Flucke, U.E.; Meyer-Wentrup, F.A.G.

Oncotarget 8(41): 71371-71384

2017


ISSN/ISBN: 1949-2553
PMID: 29050367
DOI: 10.18632/oncotarget.19071
Accession: 059721535

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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.