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Charbel, Alphonse; Tavernar, Luca; Albrecht, Thomas; Brinkmann, Fritz; Verheij, Joanne; Roos, Eva; Vogel, Monika Nadja; Köhler, Bruno; Springfeld, Christoph; Brobeil, Alexander; Schirmacher, Peter; Singer, Stephan; Mehrabi, Arianeb; Roessler, Stephanie; Goeppert, Benjamin

Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis

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  • Medientyp: E-Artikel
  • Titel: Spatiotemporal analysis of tumour-infiltrating immune cells in biliary carcinogenesis
  • Beteiligte: Charbel, Alphonse; Tavernar, Luca; Albrecht, Thomas; Brinkmann, Fritz; Verheij, Joanne; Roos, Eva; Vogel, Monika Nadja; Köhler, Bruno; Springfeld, Christoph; Brobeil, Alexander; Schirmacher, Peter; Singer, Stephan; Mehrabi, Arianeb; Roessler, Stephanie; Goeppert, Benjamin
  • Erschienen: Springer Science and Business Media LLC, 2022
  • Erschienen in: British Journal of Cancer
  • Sprache: Englisch
  • DOI: 10.1038/s41416-022-01933-0
  • ISSN: 1532-1827; 0007-0920
  • Schlagwörter: Cancer Research ; Oncology
  • Entstehung:
  • Anmerkungen:
  • Beschreibung: <jats:title>Abstract</jats:title><jats:sec><jats:title>Background</jats:title><jats:p>Intraductal papillary neoplasms (IPN) and biliary epithelial neoplasia (BilIN) are well‐defined precursor lesions of biliary tract carcinoma (BTC). The aim of this study was to provide a comprehensive characterisation of the inflammatory microenvironment in BTC precursor lesions.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Immunohistochemistry was employed to assess tumour-infiltrating immune cells in tissue samples from patients, for whom precursor lesions were identified alongside invasive BTC. The spatiotemporal evolution of the immune microenvironment during IPN-associated carcinogenesis was comprehensively analysed using triplet sample sets of non-neoplastic epithelium, precursor lesion and invasive BTC. Immune-cell dynamics during IPN- and BilIN-associated carcinogenesis were subsequently compared.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>Stromal CD3<jats:sup>+</jats:sup>(<jats:italic>P</jats:italic> = 0.002), CD4<jats:sup>+</jats:sup>(<jats:italic>P</jats:italic> = 0.007) and CD8<jats:sup>+</jats:sup>(<jats:italic>P</jats:italic> &lt; 0.001) T cells, CD20<jats:sup>+</jats:sup>B cells (<jats:italic>P</jats:italic> = 0.008), MUM1<jats:sup>+</jats:sup>plasma cells (<jats:italic>P</jats:italic> = 0.012) and CD163<jats:sup>+</jats:sup>M2-like macrophages (<jats:italic>P</jats:italic> = 0.008) significantly decreased in IPN compared to non-tumorous biliary epithelium. Upon transition from IPN to invasive BTC, stromal CD68<jats:sup>+</jats:sup>(<jats:italic>P</jats:italic> = 0.001) and CD163<jats:sup>+</jats:sup>(<jats:italic>P</jats:italic> &lt; 0.001) macrophages significantly increased. In contrast, BilIN-driven carcinogenesis was characterised by significant reduction of intraepithelial CD8<jats:sup>+</jats:sup>T-lymphocytic infiltration from non-tumorous epithelium via BilIN (<jats:italic>P</jats:italic> = 0.008) to BTC (<jats:italic>P</jats:italic> = 0.004).</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>IPN and BilIN are immunologically distinct entities that undergo different immune-cell variations during biliary carcinogenesis. Intraepithelial CD8<jats:sup>+</jats:sup>T-lymphocytic infiltration of biliary tissue decreased already at the IPN-precursor stage, whereas BilIN-associated carcinogenesis showed a slowly progressing reduction towards invasive carcinoma.</jats:p></jats:sec>
  • Zugangsstatus: Freier Zugang