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06-09-2024 | Cholangiocarcinoma | ORIGINAL ARTICLE

Prognostic impact of the tumour microenvironment in intrahepatic cholangiocarcinoma: identification of a peritumoural fibro-immune interface

Authors: Gwladys Lubuela, Aurélie Beaufrère, Miguel Albuquerque, Camille Pignollet, Rémy Nicolle, Mickael Lesurtel, Mohamed Bouattour, Jérôme Cros, Valérie Paradis

Published in: Virchows Archiv

Abstract

The tumour microenvironment (TME) of intrahepatic cholangiocarcinoma (iCCA) is complex and plays a role in prognosis and resistance to treatments. We aimed to decipher the iCCA TME phenotype using multiplex sequential immunohistochemistry (MS-IHC) to investigate which cell types and their spatial location may affect its prognosis. This was a retrospective study of 109 iCCA resected samples. For all cases, we used an open-source software to analyse a panel of markers (αSMA, FAP, CD8, CD163) by MS-IHC for characterize the different TME cells and their location. RNA sequencing was performed to determine the main iCCA transcriptomic classes. The association of the TME composition with overall survival (OS) was assessed by univariate and multivariate analyses. A high proportion of activated fibroblasts (FAP +) was significantly associated with poor OS (HR = 2.33, 95%CI = 1.43–3.81, p = 0.001). CD8 T lymphocytes excluded from the epithelial compartment were significantly associated with worse OS (HR = 1.86, 95% CI = 1.07–3.22, p = 0.014). The combination of a high proportion of FAP + fibroblasts and CD8 T lymphocytes excluded from the epithelial compartment, observed in 21 cases (19%), was significantly associated with poor OS on univariate (HR = 2.49, 95% CI = 1.44–4.28, p = 0.001) and multivariate analyses (HR = 2.77, 95% CI = 1.56–4.92, p < 0.001). In these cases, CD8 T lymphocytes were predominantly located at the tumour/non-tumour interface (19/21, 90%), and an association with the transcriptomic inflammatory stroma class was observed (10/21, 48%). Our results confirm the TME prognostic role in iCCA, highlighting the impact in the process of spatial heterogeneity, especially cell colocalization of immune and fibroblastic cells creating a peritumoural fibro-immune interface.

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Title: Prognostic impact of the tumour microenvironment in intrahepatic cholangiocarcinoma: identification of a peritumoural fibro-immune interface
Authors: Gwladys Lubuela
Aurélie Beaufrère
Miguel Albuquerque
Camille Pignollet
Rémy Nicolle
Mickael Lesurtel
Mohamed Bouattour
Jérôme Cros
Valérie Paradis
Publication date: 06-09-2024
Publisher: Springer Berlin Heidelberg
Keywords: Cholangiocarcinoma
Cholangiocarcinoma
Published in: Virchows Archiv
Print ISSN: 0945-6317
Electronic ISSN: 1432-2307
DOI: https://doi.org/10.1007/s00428-024-03922-5

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Prognostic impact of the tumour microenvironment in intrahepatic cholangiocarcinoma: identification of a peritumoural fibro-immune interface

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