High endothelial venule is a prognostic immune-related biomarker in patients with resected intrahepatic cholangiocarcinoma

Cell Prolif. 2023 Dec;56(12):e13513. doi: 10.1111/cpr.13513. Epub 2023 Jul 3.

Abstract

Having been reported to be a crucial prognostic factor in solid tumours, the role of high endothelial venule (HEV) in intrahepatic cholangiocarcinoma (ICC) remains unclear, however. The data of ICC and healthy individuals were downloaded from the Gene Expression Omnibus (GEO), and The Cancer Genome Atlas (TCGA) databases. Meanwhile, a cutting-edge ICC high-resolution spatial transcriptome was also acquired before these data were comprehensively analysed using bioinformatics approaches. Moreover, 95 individuals with ICC who had undergone resection surgery were enrolled in this study to investigate the relationship between HEV and tumour microenvironment (TME) applying immunohistochemistry and multiple immunofluorescence techniques. The high-HEV subtype contains rich immune infiltrates including tertiary lymphoid structure (TLS), CD8+ T cells, and CD20+ B cells. Furthermore, HEV and TLS exhibited a strong relationship of spatial colocalization. Correlated with improved prognostic outcomes in ICC, the high-HEV subtype could be an independent prognostic indicator for individuals with ICC. This study revealed the association of HEV with immune function and observed a strong spatial colocalization correlation between HEV and TLS. Moreover, correlated with immunotherapeutic response, HEV could improve prognostic outcomes, which may be a potential indicator of immunotherapy pathology in ICC.

MeSH terms

  • Bile Duct Neoplasms* / surgery
  • Bile Ducts, Intrahepatic / metabolism
  • Bile Ducts, Intrahepatic / pathology
  • Biomarkers / metabolism
  • Cholangiocarcinoma* / genetics
  • Cholangiocarcinoma* / surgery
  • Humans
  • Prognosis
  • Tumor Microenvironment
  • Venules / metabolism
  • Venules / pathology

Substances

  • Biomarkers