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血浆可溶性程序性死亡配体 1 水平可预测外周 T 细胞淋巴瘤的临床反应。

Plasma soluble programmed death ligand 1 levels predict clinical response in peripheral T-cell lymphomas.

机构信息

Department of Lymphoma, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center of Cancer, Key Laboratory of Cancer Prevention and Therapy, the Sino-US Center for Lymphoma and Leukemia Research, Tianjin, China.

Department of Radiotherapy Oncology, Cangzhou Central Hospital, Hebei, China.

出版信息

Hematol Oncol. 2019 Aug;37(3):270-276. doi: 10.1002/hon.2636. Epub 2019 May 30.

Abstract

Immune checkpoints, including PD-1/PD-L1, play an important role in immunosuppression in various malignancies. Elevated levels of soluble programmed death ligand 1 (sPD-L1) are associated with worse prognosis in multiple myeloma and diffuse large B cell lymphoma. Herein, the purpose of this study is to investigate the relationships between plasma sPD-L1 levels and clinical response in peripheral T-cell lymphoma (PTCL) patients. A total of 37 PTCL patients and 20 healthy volunteers were enrolled. Peripheral blood from patients was collected prior to systemic therapy. Plasma levels of sPD-L1 and IFN-γ were measured by enzyme-linked immunosorbent assay (ELISA). PD-L1 expression in tissues was detected by immunohistochemistry (IHC). Clinical response for patients was evaluated. ONCOMINE database analyses showed that PD-L1 mRNA expression was significantly upregulated in PTCLs. The median sPD-L1 level was 0.729 ng/mL for 20 healthy volunteers and 1.696 ng/mL for 37 PTCL patients which was significantly higher than that in healthy volunteers (0.000). The sPD-L1 level was positively correlated with IFN-γ level (0.000, r = 0.849) and was also positively associated with clinical staging (0.045), LDH level (0.003), and β2-MG level (0.045). Patients with high sPD-L1 level had lower overall response rate than those with low sPD-L1 level (88.9% vs 50.0%, 0.022) and tended to have poorer PFS and OS. PD-L1 expression in tissues matched very well with the sPD-L1 level in PTCL patients. In conclusion, PTCL patients had higher sPD-L1 level compared with healthy volunteers. High sPD-L1 level was correlated with worse clinical response, suggesting that sPD-L1 level was an underlying plasma biomarker to predict the prognosis for PTCL patients.

摘要

免疫检查点,包括 PD-1/PD-L1,在各种恶性肿瘤的免疫抑制中发挥重要作用。可溶性程序性死亡配体 1(sPD-L1)水平升高与多发性骨髓瘤和弥漫性大 B 细胞淋巴瘤的预后较差相关。在此,本研究旨在探讨外周 T 细胞淋巴瘤(PTCL)患者血浆 sPD-L1 水平与临床反应之间的关系。共纳入 37 例 PTCL 患者和 20 名健康志愿者。患者在全身治疗前采集外周血。采用酶联免疫吸附试验(ELISA)检测血浆 sPD-L1 和 IFN-γ水平。采用免疫组织化学(IHC)检测组织中 PD-L1 表达。评估患者的临床反应。ONCOMINE 数据库分析显示,PTCL 中 PD-L1 mRNA 表达明显上调。20 名健康志愿者的 sPD-L1 中位水平为 0.729ng/mL,37 名 PTCL 患者的 sPD-L1 中位水平为 1.696ng/mL,明显高于健康志愿者(0.000)。sPD-L1 水平与 IFN-γ水平呈正相关(0.000,r=0.849),与临床分期(0.045)、LDH 水平(0.003)和β2-MG 水平(0.045)呈正相关。sPD-L1 水平较高的患者总反应率低于 sPD-L1 水平较低的患者(88.9% vs 50.0%,0.022),且 PFS 和 OS 较差。组织中 PD-L1 的表达与 PTCL 患者的 sPD-L1 水平非常吻合。总之,PTCL 患者的 sPD-L1 水平高于健康志愿者。sPD-L1 水平与较差的临床反应相关,表明 sPD-L1 水平是预测 PTCL 患者预后的潜在血浆生物标志物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ff55/6771895/019f4900592d/HON-37-270-g001.jpg

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