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

Our plain-English summary of Pleural mesothelioma patients and ex-exposed asbestos workers are immunologically poor responders to oncogenic Merkel cell polyomavirus, by C. Mazziotta, C. Lanzillotti, C.F. Cervellera, et al (Translational Lung Cancer Research, 2025).

The study

• Authors: C. Mazziotta, C. Lanzillotti, C.F. Cervellera, G. Badiale, R. Libener, A. Maconi, E. Casalone, A. Allione, G. Matullo, M. Mencoboni, I. Bononi, F. Martini, J.C. Rotondo, M. Tognon
• Journal: Translational Lung Cancer Research
• Published: 2025;14(7):2611-2625
• Cited by: 1 article, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

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.

Copyright © 2025 AME Publishing Company. All rights reserved.

In plain English

This Italian cross-sectional study tested blood serum for IgG antibodies to Merkel cell polyomavirus (MCPyV), a common virus that is the main cause of Merkel cell carcinoma. Samples came from 108 pleural mesothelioma patients, 102 workers formerly exposed to asbestos, and 110 healthy subjects. Antibodies were found in 26.9% (29/108) of patients, 27.5% (28/102) of workers and 60.9% (67/110) of healthy subjects. Both groups differed significantly from healthy subjects. Total IgG levels did not differ significantly between the groups. Among workers, 5.6% (1/18) with cumulative exposure above 55 fibers/cc had antibodies, compared with 44.4% (12/27) of those with 0 to 8 fibers/cc. Antibody levels were inversely correlated with cumulative exposure and with years of exposure. Antibody status was not significantly linked to patient survival over 99 months. Viral DNA was found in 32% (16/50) of tumor samples from different patients, and in none of 15 healthy pleura samples. The authors concluded that both groups likely have a specific impairment of their immune response to the virus, possibly due to asbestos. They noted that finding viral DNA in tumors does not prove the virus causes mesothelioma.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Cross-sectional laboratory study of blood serum antibodies, with a separate analysis of tumor tissue samples
• Who was studied: Serum from 108 pleural mesothelioma patients, 102 workers formerly exposed to asbestos, and 110 healthy subjects, in Italy. Healthy-subject samples were discarded laboratory samples from University Hospital of Ferrara. A separate set of 50 pleural mesothelioma tumor specimens came from patients unrelated to the serum donors, with 15 healthy pleura specimens for comparison. Collection dates are not given.
• Exposure: Past occupational asbestos exposure; fiber types are not specified. Of the workers, 40 were collected at Villa Scassi Hospital, Genoa, and were longshoremen (dock/shipyard loading and unloading) or iron- and steel-mill workers. Cumulative exposure was estimated in fibers/cm3 of air (ff/cc) using a German Confederation of Trade Associations method adopted by the Italian Agency for Occupational Accident Insurance. Workers were grouped as 0 to 8 (n=27), 8.1 to 55 (n=57) and above 55 ff/cc (n=18).
• Main results:
  • Anti-MCPyV IgG antibodies were found in 26.9% (29/108) of mesothelioma patients, 27.5% (28/102) of asbestos-exposed workers and 60.9% (67/110) of healthy subjects. Patients versus healthy subjects and workers versus healthy subjects were both P less than 0.001.
  • Mean total IgG concentration did not differ significantly between groups: 4.29 mg/mL (SD 2.13) in patients, 5.72 (SD 2.2) in workers and 4.55 (SD 2.07) in healthy subjects (P greater than 0.05).
  • Among mesothelioma patients, antibody rates were 40% (16/40) for epithelioid, 28% (7/25) for sarcomatoid and 14% (6/43) for biphasic tumors. The biphasic rate was lower than the epithelioid rate (P=0.01).
  • Over 99 months of follow-up, survival did not differ significantly between antibody-positive and antibody-negative mesothelioma patients. Antibody status also showed no significant association with treatment regimen.
  • Among asbestos-exposed workers, antibody rates were 44.4% (12/27) at 0 to 8 ff/cc, 26.3% (15/57) at 8.1 to 55 ff/cc and 5.6% (1/18) above 55 ff/cc. The rate above 55 ff/cc was lower than at 0 to 8 ff/cc.
  • In workers, antibody levels were inversely correlated with cumulative asbestos exposure: r of minus 0.328 for the S peptide and minus 0.3862 for the F peptide, both P less than 0.001.
  • In workers, antibody levels were inversely correlated with years of asbestos exposure: r of minus 0.3015 (P=0.002) for the S peptide and minus 0.2397 (P=0.02) for the F peptide.
  • In workers, antibody levels were directly correlated with years since last asbestos exposure for the S peptide only (r of 0.2267, P=0.02).
  • MCPyV DNA was found in 32% (16/50) of mesothelioma tumor specimens and in none of the 15 healthy pleura specimens (P=0.01).
  • Among the 16 DNA-positive tumor specimens, all were positive for VP1 mRNA and 69% (11/16) were positive for LT mRNA.
  • No correlation was found between antibodies to the virus and tobacco exposure in the workers.
• The authors' conclusion: The authors concluded that both mesothelioma patients and asbestos-exposed workers are likely experiencing a specific impairment of their immune response to MCPyV, and suggested this might depend on the immunosuppressive effect of asbestos. They stated that whether MCPyV plays a role in mesothelioma remains a future area of study.
• Limitations the authors state:
  • Detecting viral DNA and mRNA in tumor specimens does not provide definitive evidence that the virus causes mesothelioma.
  • Only antibodies against viral structural (VP) antigens were measured, not antibodies against the viral oncoproteins.
  • Differences in sample size across the tumor-type subgroups might account for the histotype findings.
  • The immune response against other viruses was not investigated.

Topics

Medical terms in this study, explained in our Lexicon: Pleural Mesothelioma, Serous Cavities, Carcinogenic, Biphasic Mesothelioma, Asbestos Exposure.

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• The importance of retaining post mortem tissue--'pseudomesotheliomatous' Merkel cell carcinoma of the pleura — G.D. Leopold, R.L. Attanoos (2011)
• Sera from Patients with Malignant Pleural Mesothelioma Tested Positive for IgG Antibodies against SV40 Large T Antigen: The Viral Oncoprotein — E. Mazzoni, I. Bononi, et al. (2022)
• Circulating microRNAs found dysregulated in ex-exposed asbestos workers and pleural mesothelioma patients as potential new biomarkers — I. Bononi, M. Comar, et al. (2016)

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