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默克尔细胞多瘤病毒载量和肿瘤内CD8 +淋巴细胞浸润可预测默克尔细胞癌患者的总生存期。

Merkel Cell Polyoma Viral Load and Intratumoral CD8+ Lymphocyte Infiltration Predict Overall Survival in Patients With Merkel Cell Carcinoma.

作者信息

von der Grün Jens, Winkelmann Ria, Meissner Markus, Wieland Ulrike, Silling Steffi, Martin Daniel, Fokas Emmanouil, Rödel Claus, Rödel Franz, Balermpas Panagiotis

机构信息

Department of Radiotherapy and Oncology, University of Frankfurt, Frankfurt, Germany.

Dr. Senckenberg Institute of Pathology, University of Frankfurt, Frankfurt, Germany.

出版信息

Front Oncol. 2019 Jan 24;9:20. doi: 10.3389/fonc.2019.00020. eCollection 2019.

Abstract

Merkel cell carcinoma (MCC) is linked to the presence of clonally integrated Merkel cell polyomavirus (MCPyV) in up to 80% of the cases. The aim of the study was to determine the prognostic value of baseline MCPyV viral load and lymphocytic infiltration. MCPyV DNA prevalence, integration status and viral load were determined by specific quantitative real-time PCR in surgical specimens obtained from 49 patients with MCC treated with ( = 22, 45%) or without postoperative radiotherapy (RT). CD8+ tumor infiltrating lymphocytes (TILs) and programmed death ligand 1 (PD-L1) status were assessed using immunohistochemistry. MCPyV characteristics and immune marker expression were correlated with clinicopathological factors and overall survival (OS). Median age at diagnosis was 74 (range, 42-100); 51% of the patients were female. One-, three, and five-year OS rates were 83.8, 58.6, and 47.1%, respectively. A positive MCPyV status was associated with female gender ( = 0.042). Tumor localization (head/arms vs. trunk) positively correlated with PD-L1 status ( = 0.011) and combined CD8/PD-L1 expression ( = 0.038). Overall CD8+ infiltration was inversely associated with N-stage ( = 0.048). Stromal TILs correlated significantly with both PD-L1 expression ( = 0.010) and N-stage ( = 0.037). A high viral load (>median) was significantly associated with worse OS ( = 0.029) and high intratumoral CD8+ infiltration with improved OS for the entire cohort ( = 0.045). These data provide important insight on the role of MCPy DNA viral load and TILs in the context of PD-L1 in patients with Merkel cell carcinoma. Future clinical studies should aim to explore the effect of PD-1/PD-L1 immune-checkpoint inhibitors in combination with existing radiotherapy approaches.

摘要

默克尔细胞癌(MCC)与高达80%的病例中克隆整合的默克尔细胞多瘤病毒(MCPyV)的存在有关。本研究的目的是确定基线MCPyV病毒载量和淋巴细胞浸润的预后价值。通过特异性定量实时PCR在49例接受(n = 22,45%)或未接受术后放疗(RT)的MCC患者的手术标本中测定MCPyV DNA流行率、整合状态和病毒载量。使用免疫组织化学评估CD8 +肿瘤浸润淋巴细胞(TILs)和程序性死亡配体1(PD-L1)状态。MCPyV特征和免疫标志物表达与临床病理因素和总生存期(OS)相关。诊断时的中位年龄为74岁(范围42 - 100岁);51%的患者为女性。1年、3年和5年总生存率分别为83.8%、58.6%和47.1%。MCPyV阳性状态与女性性别相关(P = 0.042)。肿瘤定位(头/臂部与躯干)与PD-L1状态呈正相关(P = 0.011)以及CD8/PD-L1联合表达呈正相关(P = 0.038)。总体CD8 +浸润与N分期呈负相关(P = 0.048)。基质TILs与PD-L1表达(P = 0.010)和N分期(P = 0.037)均显著相关。高病毒载量(>中位数)与较差的总生存期显著相关(P = 0.029),而肿瘤内高CD8 +浸润与整个队列的总生存期改善相关(P = 0.045)。这些数据为默克尔细胞癌患者中MCPy DNA病毒载量和TILs在PD-L1背景下的作用提供了重要见解。未来的临床研究应旨在探索PD-1/PD-L1免疫检查点抑制剂与现有放疗方法联合使用的效果。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/cb81/6354572/0a91bb451fcd/fonc-09-00020-g0001.jpg

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