{
  "abstract": "Background The role of gut microbes in intrahepatic cholangiocarcinoma (ICC) progression is poorly understood. We identified that Fusicatenibactersaccharivorans (F. saccharivorans) is enriched in fecal samples of ICC patients and correlates with poor clinical outcomes. Here, our study aims to investigate whether and how F. saccharivorans drives ICC progression by modulating the anti-tumor immune response.Methods The role of F. saccharivorans was identified in several mouse models, including Thioacetamide (TAA)-induced ICC in conventional and germ-free mice, hydrodynamic ICC mice and mice with orthotopic injection of ICC cell line. The immune alteration was evaluated by single-cell RNA sequencing and flow cytometry on mouse tumor tissues. These findings were further validated by in vitro co-culture experiments and in vivo CD8+ T cell depletion using anti-CD8 antibodies. The secreted protein of F. saccharivorans was identified by mass spectrometry. The immunomodulatory function of the candidate protein was subsequently verified by co-culture experiments and a subcutaneous ICC mouse model.Results F. saccharivorans accelerated TAA-induced ICC development in both conventional and germ-free mice, and facilitated ICC progression in hydrodynamic and orthotopic mouse models. Critically, immune analysis on mouse tumor tissues revealed that F. saccharivorans suppressed the cytotoxic function of CD8+ T cells, as evidenced by reduced IFN-γ and Granzyme B expression alongside increased PD-1 and TIM-3 levels. Depletion of CD8+ T cells abolished the pro-tumor effects of F. saccharivorans in vivo. Consistently, CD8+ T cells co-cultured with conditioned medium from F. saccharivorans acquired an immunosuppressive phenotype. We further identified that the immunomodulatory effect of F. saccharivorans depends on its secreted protein, Pepd.Conclusions We demonstrated that F. saccharivorans is a novel pathogenic bacterium capable of promoting ICC progression. The enriched F. saccharivorans secretes protein Pepd to suppress CD8+ T cell cytotoxic function, thereby inducing immune evasion. Our findings uncovered the F. saccharivorans/Pepd axis as a critical mediator of immune suppression in ICC and highlighted potential therapeutic targets for this malignancy.",
  "authors": [
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Qianying Zhou"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Ying Zhang"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Shimao Liu"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Yuyao Liu"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Yushan Lei"
    },
    {
      "affiliations": [
        "The First Affiliated Hospital, Sun Yat-sen University, China"
      ],
      "name": "Lixia Xu"
    }
  ],
  "title": "IDDF2026-ABS-0325 Fusicatenibacter saccharivorans promotes intrahepatic cholangiocarcinoma progression by secreting Pepd to suppress CD8+ T cells",
  "uid": "7299f58a-3de4-5eb2-ae14-e72695bf9cd2"
}