Systems serology identifies differential pan-viral seroreactivity profiles associated with healthy aging and cancer
Year: 2026
Type: article
Study design: Observational Study
Abstract: A viral exposure signature (VES) has previously been shown to predict the development of hepatocellular carcinoma (HCC) in at-risk individuals through comprehensive serological profiling using the VirScan platform. Whether cumulative antimicrobial immune histories are associated with cancer status across multiple malignancies remains unknown. We applied high-throughput VirScan systems serology to characterize antibody reactivities against a comprehensive microbial peptide library in 359 participants, including 172 patients with cancer and 187 healthy individuals. To account for age-related immune remodeling, healthy participants were stratified into adults ( < 70 years) and exceptionally healthy elderly individuals ( > 80 years, including nonagenarians and centenarians). Differential Pan-viral Seroreactivity Profiles (DPSPs) were identified through an unbiased statistical workflow combining differential class comparison, feature selection, predictive modeling, cross-validation, and receiver operating characteristic (ROC) curve analysis. Distinct DPSPs discriminated healthy individuals from patients with cancer. The identified signatures comprised antibody reactivities against peptides derived predominantly from persistent herpesviruses, acute respiratory viruses and, consistently across multiple comparisons, human respiratory syncytial virus (HRSV). Remarkably, healthy elderly individuals generally exhibited higher antibody titers than patients with cancer, whereas healthy adults showed the opposite pattern. These differential serological signatures supported accurate class prediction in several comparisons, indicating that cumulative antimicrobial immune histories differ according to health status after accounting for physiological immune aging. Our findings demonstrate that lifelong cumulative antimicrobial immune history generates reproducible serological signatures associated with healthy aging and cancer status. Although the present cross-sectional study does not establish causal biological protection, it identifies hypothesis-generating biomarkers that warrant validation in independent prospective cohorts and supports the potential value of comprehensive serological profiling for future cancer risk stratification.
Source: Cell Death and Disease
Authors: Beatrice Cavalluzzo, Biancamaria Cembrola, Simona Mangano, Andre Belli, Francesco Izzo, Rosa D’Angelo, Maria Grazia Chiofalo, Cira Antonietta Forte, Alessandro Morabito, Alessandra Calabrese, Michelino De Laurentis, Vito Vanella, Paolo Ascierto, Fernanda Picozzi, Ottavia Clemente, Nicola Martucci, Ettore Pavone, Antonio Avallone, Anna Nappi, Edoardo Mercadante, Franco Ionna, Maria Cristina Lucarelli, Angela Mauriello, Concetta Ragone, Limin Wang, Changzhi Ma, Yongmei Zhao, Xin Wei Wang, Maria Tagliamonte, Luigi Buonaguro
Institutions: Istituto Nazionale Tumori IRCCS "Fondazione G. Pascale", Federico II University Hospital, National Cancer Institute, University of Molise, Villa Pineta Hospital, University of Sannio, National Cancer Institute, Center for Cancer Research, Frederick National Laboratory for Cancer Research
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
Estimated APC paid: $4,990
OpenAlex ID: W7204520266
FWCI:
Cites:
Cited by:
Related to: