Translational lung cancer research · 2025
Pleural mesothelioma patients and ex-exposed asbestos workers are immunologically poor responders to oncogenic Merkel cell polyomavirus.
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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
Аннотация
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.
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.