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Characterization of PD-1/PD-L1 immune checkpoint expression in soft tissue sarcomas
European Journal of Histochemistry ( IF 2 ) Pub Date : 2021-07-02 , DOI: 10.4081/ejh.2021.3203
Kazuhiko Hashimoto 1 , Shunji Nishimura 1 , Tomohiko Ito 1 , Masao Akagi 1
Affiliation  

Inhibitors of the programmed death-1/programmed death-ligand 1 (PD-1/PD-L1) immune checkpoint system are used for treating various malignancies. However, evidence on their use in soft tissue sarcomas (STS) is limited. This study aimed to retrospectively investigate the relationship between the expression of PD-1/PD-L1 and related antigens in STS, and their association with clinical characteristics. Immunostaining for CD4, CD8, PD-1, PD-L1, IL-2, and IFN-γ was performed using pathological specimens harvested at the time of biopsy from 10 patients with undifferentiated pleomorphic sarcoma (UPS), nine with myxofibrosarcoma (MFS), and three with malignant peripheral nerve sheath tumor (MPNST) who were treated at our hospital. Subsequently, the positive immunostaining cell rates were calculated. We also examined the correlation between each immune positive cell rate and age, tissue grade, size, and maximum standardized uptake (SUV-max) values. The 3-year event-free survival (EFS) and overall survival (OS) rates were compared between the positive and negative groups (positive rate >10%; negative <10%) for various immune stains. The positive rates were also compared between the presence and absence of events groups. There was positive staining for the immune checkpoint molecules in every STS type except for PD-1 in MPNST. CD4, CD8, and PD-1 stained lymphocytes in close proximity to the tumor in adjacent tissue sections. A positive correlation was observed between the positive cell rates of each immune component including inflammatory cytokines such as IL-2 and IFN-γ. Additionally, the clinical features positively correlated with the positive PD-1/PD-L1 expression rates. No significant differences in the 3-EFS and OS rates was observed between the PD-1/PD-L1 positive and negative groups. Our results suggest that an inducible immune checkpoint mechanism may be involved in UPS, MFS, and MPNST.



中文翻译:

软组织肉瘤中 PD-1/PD-L1 免疫检查点表达的表征

程序性死亡 1/程序性死亡配体 1 (PD-1/PD-L1) 免疫检查点系统的抑制剂用于治疗各种恶性肿瘤。然而,关于它们在软组织肉瘤 (STS) 中使用的证据是有限的。本研究旨在回顾性研究 STS 中 PD-1/PD-L1 及其相关抗原的表达及其与临床特征的关系。CD4、CD8、PD-1、PD-L1、IL-2 和 IFN-γ 的免疫染色是使用活检时从 10 名未分化多形性肉瘤 (UPS) 患者和 9 名粘液纤维肉瘤 (MFS) 患者中采集的病理标本进行的, 以及在我院接受治疗的 3 例恶性周围神经鞘瘤 (MPNST)。随后,计算阳性免疫染色细胞率。我们还检查了每个免疫阳性细胞率与年龄、组织等级、大小和最大标准化摄取 (SUV-max) 值之间的相关性。比较了各种免疫染色阳性组和阴性组(阳性率>10%;阴性<10%)的3年无事件生存率(EFS)和总生存率(OS)率。还比较了存在和不存在事件组的阳性率。除 MPNST 中的 PD-1 外,每种 STS 类型中的免疫检查点分子均呈阳性染色。CD4、CD8 和 PD-1 染色了邻近组织切片中靠近肿瘤的淋巴细胞。观察到每种免疫成分的阳性细胞率之间呈正相关,包括炎性细胞因子,如 IL-2 和 IFN-γ。此外,临床特征与 PD-1/PD-L1 阳性表达率呈正相关。在 PD-1/PD-L1 阳性组和阴性组之间未观察到 3-EFS 和 OS 率的显着差异。我们的结果表明,UPS、MFS 和 MPNST 可能涉及诱导型免疫检查点机制。

更新日期:2021-07-02
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