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. Overall design: Single cell RNA-sequencing and TCR sequencing” was performed on non-treated peripheral blood mononuclear cells (PBMCs) and CE1-treated PBMCs

肝细胞癌（hepatocellular carcinoma, HCC）是全球范围内负担沉重的癌症，其发病率逐年升高，且由于病因复杂，尚无统一的预防策略。本研究通过微生物噬菌体文库对2647名研究对象的全病毒血清抗体谱进行分析，发现与健康个体相比，肝细胞癌患者针对一组独特病毒抗原的血清学应答水平显著降低。此外，慢性肝病及肝细胞癌患者对上述病毒抗原的血清学应答水平越高，其临床预后越好。该研究结果在按性别、种族及病因划分的不同人群中均保持一致。本研究鉴定出在高流行率的鼻病毒科和肠道病毒科的反应性病毒抗原中共享的共同表位（CE1）。实验证实，CE1可诱导T细胞活化并杀伤肝细胞癌细胞。本研究结果提示，既往暴露于肠道病毒属成员或可使癌症患者获益，这凸显了基于病毒肽段的肝细胞癌疫苗的研发潜力。实验整体设计：对未经处理的外周血单个核细胞（peripheral blood mononuclear cells, PBMC）以及经CE1处理的外周血单个核细胞开展了单细胞RNA测序（single cell RNA-sequencing）与T细胞受体测序（TCR sequencing）。