Department of Anatomic Pathology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan.
Department of Orthopedic Surgery, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812‑8582, Japan.
Oncol Rep. 2021 Jan;45(1):379-389. doi: 10.3892/or.2020.7837. Epub 2020 Nov 5.
The prognosis of undifferentiated pleomorphic sarcoma (UPS) is generally unfavorable. Recently, clinical trials such as SARC028 demonstrated the utility of cancer immunotherapy for soft tissue sarcomas. The aim of the present study was to assess the expression of PD‑L1 and IDO‑1 as prognostic factors and therapeutic targets. A total of 52 primary UPS cases were retrieved and two UPS cell lines were utilized for supplementary analysis. Immunohistochemical staining of anti‑PD‑L1 (28‑8), IDO‑1, CD8, CD4, CD3, HLA class I, MSH2, MSH6, MLH1 and PMS2 was carried out. Immunohistochemically, 19 of 52 (36.5%) cases showed PD‑L1 expression at least focally (≥1%) and 5 of 52 (9.62%) showed strong PD‑L1 expression (≥50%). Overall, 25 of 52 (48.1%) cases expressed IDO‑1 (≥1%). Two tumors were evaluated as having deficient mismatch repair and six tumors as having the loss of HLA class I. PD‑L1 expression (≥1%) was significantly related to the infiltration of CD8‑ and CD3‑positive lymphocytes, but strong PD‑L1 expression (≥50%) did not present a significant relationship with tumor‑infiltrating lymphocytes. IDO‑1 expression was also associated with CD8‑, CD4‑, and CD3‑positive lymphocytes. In vitro, both PD‑L1 and IDO‑1 were induced by IFN‑γ stimulation. In survival analysis, strong PD‑L1 expression (≥50%) was a significant poor prognostic factor, while IDO‑1 expression (≥1%) was a favorable one. In conclusion, UPS was shown to frequently express PD‑L1 and IDO‑1. It was suggested that PD‑L1 expression (≥50%) and IDO‑1 expression are poor and favorable prognostic factors of UPS patients, respectively.
未分化多形性肉瘤(UPS)的预后通常较差。最近,SARC028 等临床试验表明癌症免疫疗法对软组织肉瘤有效。本研究旨在评估 PD-L1 和 IDO-1 的表达作为预后因素和治疗靶点。共检索了 52 例原发性 UPS 病例,并利用 2 种 UPS 细胞系进行了补充分析。进行了抗 PD-L1(28-8)、IDO-1、CD8、CD4、CD3、HLA Ⅰ类、MSH2、MSH6、MLH1 和 PMS2 的免疫组织化学染色。免疫组化结果显示,52 例病例中 19 例(36.5%)至少局灶性表达 PD-L1(≥1%),52 例病例中 5 例(9.62%)强表达 PD-L1(≥50%)。总体而言,52 例病例中有 25 例(48.1%)表达 IDO-1(≥1%)。2 例肿瘤被评估为错配修复缺陷,6 例肿瘤 HLA Ⅰ类缺失。PD-L1 表达(≥1%)与 CD8-和 CD3-阳性淋巴细胞浸润显著相关,但强 PD-L1 表达(≥50%)与肿瘤浸润淋巴细胞无显著相关性。IDO-1 表达也与 CD8-、CD4-和 CD3-阳性淋巴细胞相关。在体外,IFN-γ 刺激均可诱导 PD-L1 和 IDO-1 的表达。在生存分析中,强 PD-L1 表达(≥50%)是一个显著的不良预后因素,而 IDO-1 表达(≥1%)是一个有利的预后因素。综上所述,UPS 常表达 PD-L1 和 IDO-1。提示 PD-L1 表达(≥50%)和 IDO-1 表达分别是 UPS 患者不良和有利的预后因素。