van Erp Anke E M, Versleijen-Jonkers Yvonne M H, Hillebrandt-Roeffen Melissa H S, van Houdt Laurens, Gorris Mark A J, van Dam Laura S, Mentzel Thomas, Weidema Marije E, Savci-Heijink C Dilara, Desar Ingrid M E, Merks Hans H M, van Noesel Max M, Shipley Janet, van der Graaf Winette T A, Flucke Uta E, Meyer-Wentrup Friederike A G
Department of Medical Oncology, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Tumor Immunology, Radboud Institute of Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Oncotarget. 2017 Jul 7;8(41):71371-71384. doi: 10.18632/oncotarget.19071. eCollection 2017 Sep 19.
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 ( = 46), Ewing sarcoma ( = 32), alveolar rhabdomyosarcoma ( = 20), embryonal rhabdomyosarcoma ( = 77), synovial sarcoma ( = 22) and desmoplastic small round cell tumors (DSRCT) ( = 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.
为了探索免疫检查点阻断在肉瘤中的潜力，我们调查了208例肉瘤患者肿瘤中程序性细胞死亡蛋白1（PD-1）、程序性死亡配体1（PD-L1）和CD8的表达及临床相关性。对原发性未经治疗的骨肉瘤（n = 46）、尤因肉瘤（n = 32）、肺泡型横纹肌肉瘤（n = 20）、胚胎型横纹肌肉瘤（n = 77）、滑膜肉瘤（n = 22）和促纤维组织增生性小圆细胞肿瘤（DSRCT）（n = 11）进行免疫组织化学检查。PD-L1表达主要在肺泡型和胚胎型横纹肌肉瘤中检测到（分别为15%和16%）。在肺泡型亚型中，PD-L1表达与更好的总生存期、无事件生存期和无转移生存期相关。淋巴细胞上的PD-1表达主要见于滑膜肉瘤（18%）。高水平的CD8 +淋巴细胞主要在骨肉瘤中检测到（35%），并与滑膜肉瘤较差的无事件生存期相关。尤因肉瘤和DSRCT在肿瘤细胞上显示PD-1，而不是在肿瘤浸润淋巴细胞上。总体而言，发现表达及临床相关性具有亚型依赖性。首次描述了尤因肉瘤（19%）和DSRCT（82%）肿瘤细胞上的PD-1表达。
