{
  "abstract": "Background Liver transplantation (LT) is the most effective treatment for hepatocellular carcinoma (HCC), yet preventing post-transplant recurrence remains an unmet challenge. While our group and others have identified ischemia-reperfusion injury (IRI) as a key recurrence driver, the relevance of neuro-immune crosstalk, an emerging oncology paradigm, to post-LT recurrence remains unclear.Methods We analyzed clinical LT and HCC resection cohorts from Queen Mary Hospital. In the LT cohort, we evaluated IRI-induced neural alterations and compared post-reperfusion graft immune microenvironments between recipients with and without recurrence. The resection cohort included tumor-adjacent tissues from primary resection (with vs. without subsequent recurrence) and secondary surgery for recurrent disease. In vivo, a C57BL/6 mouse HCC model mapped the 3D spatial distribution of hepatic nerves and immune components, while a Sprague-Dawley rat LT model profiled temporal neuro-immune interactions post-transplantation. TCGA datasets validated their prognostic significance.Results Post-LT HCC recurrence correlated with severe parenchymal injury and impaired hepatic innervation. Recurrent grafts exhibited elevated nerve injury markers (ATF3) alongside reduced regeneration markers (GAP43) ( IDDF2026-ABS-0381 Figure 1(A) Influence of IRI on the Hepatic Nervous System). A rat LT model with high IRI (small grafts) showed increased ATF3 and delayed tyrosine hydroxylase (TH) nerve regeneration versus low IRI (whole grafts) (IDDF2026-ABS-0381 Figure 1(B) Influence of IRI on the Hepatic Nervous System). Mechanistically, in resection cohorts, nerve growth factor (NGF) and TH were significantly lower in patients with recurrence, decreasing further at secondary resection and correlating with shorter survival in the TCGA database (IDDF2026-ABS-0381 Figure 2. Impact of neural alterations on HCC recurrence and survival). Furthermore, recurrence featured immune depletion and diminished neuro-immune signaling, with marked loss of TH+ nerve fiber and CD3+ T cell colocalization versus normal livers (IDDF2026-ABS-0381 Figure 3(A) Interaction between neural signaling and the immune microenvironment is mediated by activated ADRA1). Transcriptomic screening of receptors in TCGA (normal vs. tumor) and our LT cohort identified ADRA1B as the key neural target, with its prognostic value further validated by TCGA survival and HCC resection data (IDDF2026-ABS-0381 Figure 3(B) Interaction between neural signaling and the immune microenvironment is mediated by activated ADRA1). Spatial and expression analyses revealed ADRA1B predominantly colocalized with CD3+ T cells, indicating that diminished signaling via ADRA1B+ CD3+ T cells modulates the microenvironment to facilitate recurrence (IDDF2026-ABS-0381 Figure 3(C) Interaction between neural signaling and the immune microenvironment is mediated by activated ADRA1).Conclusions An IRI-induced reduction in nerve activity correlates with decreased ADRA1B expression on CD3 + T cells and increased HCC recurrence post-LT. These findings suggest impaired neural signaling fosters an immunosuppressive microenvironment promoting recurrence.Abstract IDDF2026-ABS-0381 Figure 1Abstract IDDF2026-ABS-0381 Figure 2Abstract IDDF2026-ABS-0381 Figure 3",
  "authors": [
    {
      "affiliations": [
        "The University of Hong Kong, China"
      ],
      "name": "Yuanjin Lyu"
    },
    {
      "affiliations": [
        "The University of Hong Kong, China"
      ],
      "name": "Jiang Liu"
    },
    {
      "affiliations": [
        "The University of Hong Kong, China"
      ],
      "name": "Albert Chi-Yan Chan"
    },
    {
      "affiliations": [
        "The University of Hong Kong, China"
      ],
      "name": "Kwan Man"
    }
  ],
  "title": "IDDF2026-ABS-0381 Diminished alpha-adrenergic neuro-immune signaling drives hepatocellular carcinoma recurrence post-liver transplantation",
  "uid": "0379b35d-d6d4-5923-b8fb-805d808e7a19"
}