Yonsei Cancer Center, Division of Medical Oncology, Department of Internal Medicine, Yonsei University College of Medicine, Seoul, South Korea
Chan Kim , Eun Kyung Kim , Jung Woo Han , Hong Jae Chon , Su Jin Heo , Young Han Lee , Yong Jin Cho , Jin-Suck Suh , Kyoo-Ho Shin , Joong Bae Ahn , Hyun Cheol Chung , Sun Young Rha , Soo Hee Kim , Hyo Song Kim
Background: PD-1/PD-L1 axis plays a paramount role in tumor immune escape by negative regulation of T-cell functions. Recently, immune checkpoint inhibitors targeting this axis displayed promising anti-tumor activity with durable response, and the predictive role of PD-L1 expression is being investigated in various solid tumors. In the present study, we aimed to characterize the PD-L1 expression pattern and its clinical implication in soft-tissue sarcomas (STS). Methods: We analyzed PD-L1 expression in 82 STS patients with 5 subtypes including rhabdomyosarcoma (n = 32), synovial sarcoma (n = 19), Ewing sarcoma (n = 18), epithelioid sarcoma (n = 7), and mesenchymal chondromsarcoma (n = 6). PD-L1 expression was evaluated using anti-PD-L1 antibody (clone 130021, R&D System), and PD-L1 positivity was defined as more than 10% of PD-L1 staining in tumor cells. PD-L1 expression was compared with other clinicopathologic variables. Results: Median age at diagnosis of patient cohort was 26 (range: 1-78) and male-to-female ratio was 1.6. Initial disease presentation was locoregional disease in 80% of patients and metastatic disease in the remaining 20%. PD-L1 expression was identified in 43% of STS patients. Histologic subtype of STS was significantly associated with PD-L1 expression (p = 0.004). Proportion of PD-L1 expressing tumors was highest in epithelioid sarcoma (100%, 7/7), followed by synovial sarcoma (53%, 10/19), rhabdomyosarcoma (38%, 12/32), and Ewing sarcoma (33%, 6/18), while it was not expressed in mesenchymal chondrosarcoma (0%, 0/6). Baseline clinical characteristics other than histologic subtype was not correlated with PD-L1 expression. Patients with PD-L1 expression had worse overall survival compared with those without PD-L1 expression (5-year survival rate: 48% in PD-L1 positive vs. 68% in PD-L1 negative, p = 0.015). Moreover, this negative prognostic role of PD-L1 expression in STS was also confirmed by multivariate analysis with Cox regression model (HR: 2.67, p = 0.017). Conclusions: PD-L1 is not only expressed in STS but also stand as an independent negative prognostic factor for overall survival of STS patients. Thus, PD-L1 needs to be pursued as a potential therapeutic target in patients with STS.
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