The immune microenvironment of uterine adenosarcomas.

Clinical Sarcoma Research Pub Date : 2020-03-28 eCollection Date: 2020-01-01 DOI:10.1186/s13569-020-0127-0
Ali Mohammed Refaat Ali, Jen-Wei Tsai, Cheuk Hong Leung, Heather Lin, Vinod Ravi, Anthony P Conley, Alexander J Lazar, Wei-Lien Wang, Michael J Nathenson
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Abstract

Background: Uterine adenosarcoma (UA) is an extremely rare sarcoma subtype. There has been limited evaluation of the immune microenvironment in these tumors. The objective of this study is to examine and describe the immune infiltrate and PD-1/PD-L1 expression in UA and to correlate these changes in the tumor micro-environment with the overall survival status or the disease-free survival status (DFSS), respectively.

Methods: Patients (pts) treated at our center from 1982 to 2014 with UA were identified. Fifteen cases had tumor paraffin-embedded blocks available. Immunohistochemistry studies for CD3, CD8, FOXP3, CD163, PD-1 and PD-L1 (clone 22C3) were performed. Image analysis was used to assess the density (cells/mm2), except in PD-L1, where the percentage of membranous staining on tumor cells was noted.

Results: Immune infiltrate analysis median (range) density in cells/mm2 varied broadly: CD3 178 (15-802); CD8 117 (11-661); FoxP3 4.8 (0.2-82); CD163 791 (264-1861); and PD1 5 (1-65). 3 cases had rare (1%) PD-L1 tumor membranous labeling. The reports yielded that ten pts were alive, and 5 were dead. Pts who were alive had significant higher CD3 and CD8 median densities in tumors than those who were dead (p = 0.040). There was no correlation between DFSS and CD3 or CD8 median densities. Patients who had no local recurrence had significantly higher CD3 and CD8 median densities in tumors than those who had local recurrence (p = 0.040).

Conclusions: In conclusion, this is the first report characterizing the presence of immune infiltrate and PD-1/PD-L1 expression in UA. CD3+ CD8+ T-cells density may be prognostic. The immune-responsiveness of UA needs to be further investigated in a larger study.

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子宫腺肉瘤的免疫微环境。
背景:子宫腺肉瘤(UA)是一种极为罕见的肉瘤亚型:子宫腺肉瘤(UA)是一种极为罕见的肉瘤亚型。对此类肿瘤免疫微环境的评估十分有限。本研究旨在检查和描述 UA 中的免疫浸润和 PD-1/PD-L1 表达,并将这些肿瘤微环境变化分别与总生存状况或无病生存状况(DFSS)相关联:确定1982年至2014年在本中心接受治疗的UA患者(pts)。其中15例有肿瘤石蜡包埋块。对CD3、CD8、FOXP3、CD163、PD-1和PD-L1(克隆22C3)进行免疫组化研究。图像分析用于评估密度(细胞/平方毫米),但 PD-L1 除外,图像分析记录的是肿瘤细胞膜染色的百分比:结果:免疫浸润分析的中位(范围)密度(细胞/mm2)差异很大:CD3 178 (15-802);CD8 117 (11-661);FoxP3 4.8 (0.2-82);CD163 791 (264-1861);PD1 5 (1-65)。3例罕见(1%)PD-L1肿瘤膜状标记。报告显示,10 例患者存活,5 例死亡。与死亡病例相比,存活病例肿瘤中 CD3 和 CD8 中位密度明显更高(P = 0.040)。DFSS 与 CD3 或 CD8 中位密度之间没有相关性。无局部复发患者肿瘤中 CD3 和 CD8 中位密度明显高于局部复发患者(p = 0.040):总之,这是第一份描述UA中免疫浸润和PD-1/PD-L1表达的报告。CD3+ CD8+ T细胞密度可能预示着预后。尿毒症的免疫反应性需要在更大规模的研究中进一步调查。
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期刊介绍: Clinical Sarcoma Research considers for publication articles related to research on sarcomas, including both soft tissue and bone. The journal publishes original articles and review articles on the diagnosis and treatment of sarcomas along with new insights in sarcoma research, which may be of immediate or future interest for diagnosis and treatment. The journal also considers negative results, especially those from studies on new agents, as it is vital for the medical community to learn whether new agents have been proven effective or ineffective within subtypes of sarcomas. The journal also aims to offer a forum for active discussion on topics of major interest for the sarcoma community, which may be related to both research results and methodological topics.
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