胸膜间皮瘤患者和曾经接触过石棉的工人对致癌性默克尔细胞多瘤病毒的免疫反应较差。

Pleural mesothelioma patients and ex-exposed asbestos workers are immunologically poor responders to oncogenic Merkel cell polyomavirus.

作者信息

Mazziotta Chiara, Lanzillotti Carmen, Cervellera Christian Felice, Badiale Giada, Libener Roberta, Maconi Antonio, Casalone Elisabetta, Allione Alessandra, Matullo Giuseppe, Mencoboni Manlio, Bononi Ilaria, Martini Fernanda, Rotondo John Charles, Tognon Mauro

机构信息

Department of Medical Sciences, Laboratories of Cell Biology and Molecular Genetics, School of Medicine, University of Ferrara, Ferrara, Italy.

Center for Studies on Gender Medicine, Department of Medical Sciences, University of Ferrara, Ferrara, Italy.

出版信息

Transl Lung Cancer Res. 2025 Jul 31;14(7):2611-2625. doi: 10.21037/tlcr-2025-198. Epub 2025 Jul 28.

DOI:10.21037/tlcr-2025-198

PMID:40799442

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12337077/

Abstract

BACKGROUND

Pleural mesothelioma (PM) is an aggressive tumor of the serous cavities primarily caused by the inhalation of asbestos, a carcinogenic and immunomodulatory mineral. Other factors, such as oncogenic viruses, might be involved in PM onset. Merkel cell polyomavirus (MCPyV) is a ubiquitous oncogenic DNA virus whose increased activity has been documented in conditions of immunosuppression. In this study, we aimed to investigate the immunological response to MCPyV in PM patients and workers ex-exposed to asbestos (WEA).

METHODS

MCPyV serology was investigated herein in sera from 108 PM patients, 102 WEA, and 110 healthy subjects (HS). Total serum immunoglobulin G (IgG) levels were evaluated. The presence of MCPyV DNA and viral protein (VP)1 and large T (LT) messenger RNAs (mRNAs) was evaluated by droplet-digital polymerase chain reaction (ddPCR)/quantitative polymerase chain reaction (qPCR) in 50 tumor specimens from PM patients unrelated to PM serum donors.

RESULTS

Reduced serum anti-MCPyV IgG rates and optical densities (ODs) were detected in PM (26.9% and 0.08-0.09) and WEA (27.5% and 0.08-0.09) compared to HS (60.9% and 0.16-0.33) (P<0.001), while the mean total IgG concentrations were similar among groups (4.3-5.7 mg/mL) (P>0.05). Biphasic PM histotype exhibited the lowest MCPyV IgG levels. WEAs with the highest asbestos exposure had the lowest rate and ODs of serum anti-MCPyV IgGs (5.6% and 0.074-0.083) in contrast to WEA (44.4% and 0.083-0.096) with lower exposure. Spearman analyses revealed an inverse correlation between ODs and both cumulative asbestos exposure and years of asbestos exposure (P<0.05), while a direct correlation was detected between years since last exposure and ODs (P=0.02). MCPyV DNA was detected in 32% of PM specimens with a mean viral DNA load of 0.39±0.2 copy/cell. VP1 mRNA was detected in all MCPyV DNA-positive PMs, while 69% of these specimens tested LT mRNA-positive.

CONCLUSIONS

Our study provides the first evidence that PM and WEA may experience a specific impairment of their immune response to MCPyV. This might possibly depend on the immunomodulatory effect of asbestos, a well-known immunosuppressive mineral.

摘要

背景

胸膜间皮瘤（PM）是一种发生于浆膜腔的侵袭性肿瘤，主要由吸入石棉所致，石棉是一种具有致癌性和免疫调节作用的矿物质。其他因素，如致癌病毒，可能也参与了PM的发病过程。默克尔细胞多瘤病毒（MCPyV）是一种普遍存在的致癌DNA病毒，其活性增加已在免疫抑制状态下得到证实。在本研究中，我们旨在调查PM患者和既往接触过石棉的工人（WEA）对MCPyV的免疫反应。

方法

本研究检测了108例PM患者、102例WEA和110例健康受试者（HS）血清中的MCPyV血清学情况。评估了血清总免疫球蛋白G（IgG）水平。通过液滴数字聚合酶链反应（ddPCR）/定量聚合酶链反应（qPCR）检测了50例与PM血清供体无关的PM患者肿瘤标本中MCPyV DNA、病毒蛋白（VP）1和大T（LT）信使核糖核酸（mRNA）的存在情况。

结果

与HS（60.9%和0.16 - 0.33）相比，PM组（26.9%和0.08 - 0.09）和WEA组（27.5%和0.08 - 0.09）血清抗MCPyV IgG率和光密度（OD）降低（P<0.001），而各组间总IgG平均浓度相似（4.3 - 5.7 mg/mL）（P>0.05）。双相PM组织学类型的MCPyV IgG水平最低。石棉暴露量最高的WEA血清抗MCPyV IgGs率和OD最低（5.6%和0.074 - 0.083），而暴露量较低的WEA为（44.4%和0.083 - 0.096）。Spearman分析显示OD与累积石棉暴露量和石棉暴露年限均呈负相关（P<0.05），而与上次暴露后的年限呈正相关（P = 0.02）。32%的PM标本中检测到MCPyV DNA，平均病毒DNA载量为0.39±0.2拷贝/细胞。所有MCPyV DNA阳性的PM标本中均检测到VP1 mRNA，其中69%的标本LT mRNA检测为阳性。