Wunder Jay S, Lee Minji J, Nam Junghyun, Lau Beatrice Y, Dickson Brendan C, Pinnaduwage Dushanthi, Bull Shelley B, Ferguson Peter C, Seto Andrew, Gokgoz Nalan, Andrulis Irene L
University of Toronto Musculoskeletal Oncology Unit, Sinai Health System, Toronto, ON, Canada.
Lunenfeld-Tanenbaum Research Institute, Sinai Health System, Toronto, ON, Canada.
Oncoimmunology. 2020 Mar 18;9(1):1737385. doi: 10.1080/2162402X.2020.1737385.
Immune checkpoint proteins, such as PD-L1 and PD-1, are important in several cancers; however, their role in osteosarcoma (OSA) and soft tissue sarcoma (STS) remains unclear. Our aims were to determine whether subsets of OSA/STS harbor tumor-infiltrating lymphocytes (TILs) and express PD-L1, and how PD-L1 expression is related to clinical outcome. Tissue sections of 25 cases each of untreated undifferentiated pleomorphic sarcoma (UPS), myxofibrosarcoma (MFS), liposarcoma (LPS) and 24 of leiomyosarcoma (LMS) were subjected to immunohistochemistry (IHC) for immune cells, PD-L1 and PD-1. RT-qPCR was utilized to quantify levels of PD-L1 mRNA from 33 UPS, 57 MFS and 79 OSA primary-untreated specimens. PD-L1 mRNA levels were tested for their correlation with overall survival in patients presenting without metastases. Transcriptome analysis evaluated biological pathway differences between high and low PD-L1 expressers. A subset of UPS and MFS contained TILs and expressed PD-L1 and PD-1; LMS and LPS did not. PD-L1 levels by IHC and RT-qPCR were positively correlated. PD-L1 over-expression was associated with better survival for UPS and OSA, but not MFS. The Th1 pathway was significantly activated in UPS with high levels of PD-L1 and improved survival. Some sarcoma subtypes harbor TILs and express PD-L1. Patients with UPS and OSA with high levels of PD-L1 had better overall survival than those with low expression levels. Important biological pathways distinguish PD-L1 high and low groups. The stratification of patients with OSA/STS with respect to potential immune therapies may be improved through investigation of the expression of immune cells and checkpoint proteins.
免疫检查点蛋白，如程序性死亡受体配体1（PD-L1）和程序性死亡蛋白1（PD-1），在多种癌症中具有重要作用；然而，它们在骨肉瘤（OSA）和软组织肉瘤（STS）中的作用仍不清楚。我们的目的是确定OSA/STS的亚组是否含有肿瘤浸润淋巴细胞（TILs）并表达PD-L1，以及PD-L1表达与临床结果之间的关系。对25例未治疗的未分化多形性肉瘤（UPS）、黏液纤维肉瘤（MFS）、脂肪肉瘤（LPS）以及24例平滑肌肉瘤（LMS）的组织切片进行免疫细胞、PD-L1和PD-1的免疫组织化学（IHC）检测。利用逆转录定量聚合酶链反应（RT-qPCR）对33例UPS、57例MFS和79例未经治疗的OSA原发标本中的PD-L1 mRNA水平进行定量。检测PD-L1 mRNA水平与无转移患者总生存期的相关性。转录组分析评估高表达和低表达PD-L1者之间的生物学途径差异。UPS和MFS的一个亚组含有TILs并表达PD-L1和PD-1；LMS和LPS则不然。免疫组织化学和RT-qPCR检测的PD-L1水平呈正相关。PD-L1过表达与UPS和OSA的较好生存期相关，但与MFS无关。在PD-L1水平高且生存期改善的UPS中，Th1途径被显著激活。一些肉瘤亚型含有TILs并表达PD-L1。PD-L1水平高的UPS和OSA患者的总生存期优于低表达水平者。重要的生物学途径区分了PD-L1高表达组和低表达组。通过研究免疫细胞和检查点蛋白的表达，可能会改善OSA/STS患者在潜在免疫治疗方面的分层。
