Beneficial infections of the enterovirus genus in patients with liver cancer

Hepatocellular carcinoma (HCC) is a significant global cancer burden, with raising incidence and lacks a unified prevention strategy due to complex etiologies. By profiling pan-viral serological antibody repertoires using a microbial phage library among 2,647 study subjects, we have identified a unique set of viral antigens with a significantly reduced serological response in HCC patients compared to healthy individuals. Additionally, a higher serological response to these viral antigens links to better clinical outcomes of patients with chronic liver diseases and HCC. These findings are consistent across different populations across sex, ethnicity, and etiology. We have identified a common epitope (CE1) shared among reactive viral antigens from the highly prevalent rhinovirus and enterovirus families. We demonstrate that CE1 induces T-cell activation and HCC cell killing. Our results suggest that past exposures to members of the Enterovirus genus may be advantageous for cancer patients, highlighting the potential for a viral peptide-based HCC vaccine. Single cell RNA-sequencing and TCR sequencing” was performed on non-treated peripheral blood mononuclear cells (PBMCs) and CE1-treated PBMCs