Beneficial infections of the enterovirus genus in patients with liver cancer.

Abstract

Hepatocellular carcinoma (HCC) is a significant global cancer burden, with rising incidence and lacking a unified prevention strategy due to complex aetiologies. Viral exposures may shape host immunity via specific reactive viral antigens that could induce immune responses against hepatocarcinogenesis. We aimed to characterise viral exposure differences between HCC patients and healthy individuals and identify potentially protective viral antigens against HCC. We profiled pan-viral serological antibody repertoires using a microbial phage library among 2647 study subjects and examined the biological activities of selective viral antigens on blood-derived immune cells from both healthy individuals and HCC patients. We identified 153 viral antigens with a significantly reduced serological response in HCC patients compared with healthy individuals. We also observed that a higher serological response to 153 viral antigens is associated with better clinical outcomes of patients with chronic liver diseases and HCC. These findings are consistent across different populations across sex, ethnicity and aetiology. We identified a common epitope (CE1) shared among 39% of reactive viral antigens that belong to the rhinovirus and enterovirus families. We demonstrated that CE1 could induce both CD4⁺ and CD8⁺ T-cell activation and CD8⁺ T-cell-mediated 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.