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程序性死亡配体 1 的表达与骨髓肉瘤患者的不良预后相关。

Expression of programmed death ligand 1 is associated with poor prognosis in myeloid sarcoma patients.

机构信息

Department of Pathology, Kurume University School of Medicine, Kurume, Japan.

Department of Hematology, Endocrinology and Metabolism, Faculty of Medicine, Niigata University, Niigata, Japan.

出版信息

Hematol Oncol. 2018 Aug;36(3):591-599. doi: 10.1002/hon.2506. Epub 2018 Mar 30.

Abstract

Myeloid sarcoma (MS) is a rare condition and is an extramedullary tumour of immature myeloid cells. It is now known that the programmed death 1 (PD-1)/programmed death ligand 1 (PD-L1) pathway suppresses the host antitumor responses and that these products are expressed on both tumour cells and tumour-infiltrating cells in various malignancies. However, little is known about the significance of PD-1/PD-L1 expression on tumour cells and tumour microenvironmental cells in MS. To investigate the clinicopathological significance of PD-1/PD-L1 expression in MS, we analyzed 98 patients by immunohistochemistry. Of these, 10.2% of cases had neoplastic tumour cells positive for PD-L1 (nPD-L1 ). However, the rate of nPD-L1 was <5% (range: 0.27 to 2.97%). On the other hand, PD-L1 expression on 1 or more of stromal cells in the tumour microenvironment (miPD-L1 ) was observed in 37.8% of cases. Because all nPD-L1 cases expressed PD-1 on less than 5% of tumour cells, we compared the miPD-L1 and miPD-L1 groups. There was a correlation between miPD-L1 status and the number of PD-1-expressing tumour -infiltrating lymphocytes (PD-1 TILs; P = .0229). miPD-L1 was found to be associated with poorer overall survival and progression-free survival (P = .00392, P = .00261, respectively). Multivariate analysis also confirmed miPD-L1 to be an independent poor prognostic factor. In conclusion, our study indicated that the immunotherapy blocking the PD-1/PD-L1 pathway may improve the clinical outcome of MS.

摘要

骨髓肉瘤(MS)是一种罕见的疾病,是未成熟髓细胞的髓外肿瘤。现在已知程序性死亡 1(PD-1)/程序性死亡配体 1(PD-L1)途径抑制宿主抗肿瘤反应,这些产物在各种恶性肿瘤的肿瘤细胞和肿瘤浸润细胞上表达。然而,关于 PD-1/PD-L1 在 MS 中肿瘤细胞和肿瘤微环境细胞表达的意义知之甚少。为了研究 PD-1/PD-L1 表达在 MS 中的临床病理意义,我们通过免疫组织化学分析了 98 例患者。其中,10.2%的病例存在 PD-L1 阳性(nPD-L1)的肿瘤细胞。然而,nPD-L1 的比率<5%(范围:0.27-2.97%)。另一方面,在肿瘤微环境(miPD-L1)中 1 个或多个基质细胞上观察到 PD-L1 表达,占 37.8%的病例。因为所有 nPD-L1 病例的肿瘤细胞上 PD-1 表达均<5%,所以我们比较了 miPD-L1 和 miPD-L1 组。miPD-L1 状态与表达 PD-1 的肿瘤浸润淋巴细胞(PD-1 TILs)的数量之间存在相关性(P=0.0229)。miPD-L1 与总生存期和无进展生存期较差相关(P=0.00392,P=0.00261)。多变量分析也证实 miPD-L1 是独立的不良预后因素。总之,我们的研究表明,免疫治疗阻断 PD-1/PD-L1 途径可能改善 MS 的临床结果。

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