TY - JOUR
T1 - Expression and clinical association of programmed cell death-1, programmed death-ligand-1 and CD8+ lymphocytes in primary sarcomas is subtype dependent
AU - van Erp, Anke E M
AU - Versleijen-Jonkers, Yvonne M H
AU - Hillebrandt-Roeffen, Melissa H S
AU - van Houdt, Laurens
AU - Gorris, Mark A J
AU - van Dam, Laura S
AU - Mentzel, Thomas
AU - Weidema, Marije E
AU - Savci-Heijink, C Dilara
AU - Desar, Ingrid M E
AU - Merks, Hans H M
AU - van Noesel, Max M
AU - Shipley, Janet
AU - van der Graaf, Winette T A
AU - Flucke, Uta E
AU - Meyer-Wentrup, Friederike A G
N1 - Publisher Copyright:
© van Erp et al.
PY - 2017/9/19
Y1 - 2017/9/19
N2 - 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.
AB - 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.
KW - Desmoplastic small round cell tumor (DSRCT)
KW - Immune checkpoint blockade
KW - Programmed cell death-1 (PD-1)
KW - Programmed death ligand-1 (PD-L1)
KW - Sarcoma
UR - http://www.scopus.com/inward/record.url?scp=85030213220&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.19071
DO - 10.18632/oncotarget.19071
M3 - Article
C2 - 29050367
SN - 1949-2553
VL - 8
SP - 71371
EP - 71384
JO - Oncotarget
JF - Oncotarget
IS - 41
ER -