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132 例原发性皮肤 Merkel 细胞癌中肿瘤 PD-L1 和 IDO1 表达、肿瘤内 CD8+ 和 FoxP3+淋巴细胞浸润的预后作用。

Prognostic Role of Tumoral PD-L1 and IDO1 Expression, and Intratumoral CD8+ and FoxP3+ Lymphocyte Infiltrates in 132 Primary Cutaneous Merkel Cell Carcinomas.

机构信息

Department of Clinical and Experimental Pathology, Wroclaw Medical University, 50-556 Wroclaw, Poland.

Department of Pathology, National Cheng Kung University Hospital, College of Medicine, National Cheng Kung University, Tainan 70403, Taiwan.

出版信息

Int J Mol Sci. 2021 May 23;22(11):5489. doi: 10.3390/ijms22115489.

Abstract

The association of immune markers and clinicopathologic features and patient outcome has not been extensively studied in Merkel cell carcinoma (MCC). We correlated tumoral PD-L1 and IDO1 expression, and intratumoral CD8+ and FoxP3+ lymphocytes count with clinicopathologic variables, Merkel cell polyomavirus (MCPyV) status, and patient outcomes in a series of 132 MCC. By univariate analyses, tumoral PD-L1 expression >1% and combined tumoral PD-L1 >1% and high intratumoral FoxP3+ lymphocyte count correlated with improved overall survival (OS) ( = 0.016, 0.0072), MCC-specific survival (MSS) ( = 0.019, 0.017), and progression-free survival (PFS) ( = 0.043, 0.004, respectively). High intratumoral CD8+ and FoxP3+ lymphocyte count correlated with longer MSS ( = 0.036) and improved PFS ( = 0.047), respectively. Ulceration correlated with worse OS and worse MSS. Age, male gender, and higher stage (3 and 4) significantly correlated with worse survival. MCPyV positivity correlated with immune response. By multivariate analyses, only ulceration and age remained as independent predictors of worse OS; gender and stage remained for shorter PFS. Tumoral PD-L1 expression and increased density of intratumoral CD8+ lymphocytes and FoxP+ lymphocytes may represent favorable prognosticators in a subset of MCCs. Tumoral PD-L1 expression correlated with intratumoral CD8+ and FoxP3+ lymphocytes, which is supportive of an adaptive immune response.

摘要

在默克尔细胞癌(Merkel cell carcinoma,MCC)中,免疫标志物与临床病理特征和患者预后的关系尚未得到广泛研究。我们在一系列 132 例 MCC 中,将肿瘤 PD-L1 和 IDO1 的表达、肿瘤内 CD8+和 FoxP3+淋巴细胞计数与临床病理变量、Merkel 细胞多瘤病毒(Merkel cell polyomavirus,MCPyV)状态和患者预后相关联。通过单因素分析,肿瘤 PD-L1 表达>1%和联合肿瘤 PD-L1>1%和高肿瘤内 FoxP3+淋巴细胞计数与总生存期(overall survival,OS)(=0.016,0.0072)、MCC 特异性生存期(Merkel cell carcinoma-specific survival,MSS)(=0.019,0.017)和无进展生存期(progression-free survival,PFS)(=0.043,0.004)的改善相关。高肿瘤内 CD8+和 FoxP3+淋巴细胞计数与 MSS (=0.036)和 PFS(=0.047)的延长相关。溃疡与 OS 和 MSS 较差相关。年龄、男性和更高的分期(3 期和 4 期)与生存率较差显著相关。MCPyV 阳性与免疫反应相关。通过多因素分析,只有溃疡和年龄仍然是 OS 较差的独立预测因素;性别和分期仍然是 PFS 较短的独立预测因素。肿瘤 PD-L1 表达以及肿瘤内 CD8+淋巴细胞和 FoxP+淋巴细胞密度的增加可能是 MCC 亚群的有利预后指标。肿瘤 PD-L1 表达与肿瘤内 CD8+和 FoxP3+淋巴细胞相关,这支持适应性免疫反应。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e24f/8197111/6c84b7f69f3b/ijms-22-05489-g001.jpg

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