Supplementary Table 3 from Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy

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posted on 2023-03-31, 23:15 authored by Cong Trung Nguyen, Stefano Caruso, Pascale Maille, Aurélie Beaufrère, Jérémy Augustin, Loetitia Favre, Anaïs Pujals, Camille Boulagnon-Rombi, Rami Rhaiem, Giuliana Amaddeo, Luca di Tommaso, Alain Luciani, Hélène Regnault, Raffaele Brustia, Olivier Scatton, Frédéric Charlotte, Isabelle Brochériou, Daniele Sommacale, Patrick Soussan, Vincent Leroy, Alexis Laurent, Van Ky Le, Van To Ta, Hong Son Trinh, Thi Lan Tran, David Gentien, Audrey Rapinat, Jean Charles Nault, Manon Allaire, Sebastien Mulé, Jessica Zucman-Rossi, Jean-Michel Pawlotsky, Christophe Tournigand, Fouad Lafdil, Valérie Paradis, Julien Calderaro

Supplementary Table 3: Difference in gene expression between IH1 and IH2 subtypes IH: Immune - High

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Bristol-Myers Squibb Foundation

Fondation ARC

Institut National du Cancer

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ARTICLE ABSTRACT

Combined hepatocellular-cholangiocarcinoma (cHCC-CCA) is a rare malignancy associated with an overall poor prognosis. We aimed to investigate the immune profile of cHCC-CCA and determine its impact on disease outcome. We performed a multicenter study of 96 patients with cHCC-CCA. Gene expression profile was analyzed using nCounter PanCancer IO 360 Panel. Densities of main immune cells subsets were quantified from digital slides of IHC stainings. Genetic alterations were investigated using targeted next-generation sequencing. Two main immune subtypes of cHCC-CCA were identified by clustering analysis: an “immune-high” (IH) subtype (57% of the cases) and an “immune-low” (IL) subtype (43% of the cases). Tumors classified as IH showed overexpression of genes related to immune cells recruitment, adaptive and innate immunity, antigen presentation, cytotoxicity, immune suppression, and inflammation (P < 0.0001). IH cHCC-CCAs also displayed activation of gene signatures recently shown to be associated with response to immunotherapy in patients with HCC. Quantification of immunostainings confirmed that IH tumors were also characterized by higher densities of immune cells. Immune subtypes were not associated with any genetic alterations. Finally, multivariate analysis showed that the IH subtype was an independent predictor of improved overall survival. We have identified a subgroup of cHCC-CCA that displays features of an ongoing intratumor immune response, along with an activation of gene signatures predictive of response to immunotherapy in HCC. This tumor subclass is associated with an improved clinical outcome. These findings suggest that a subset of patients with cHCC-CCA may benefit from immunomodulating therapeutic approaches.

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Keywords

Gynecological Cancers Uterine cancer Immunotherapy Biomarkers for immunotherapy Tumor Microenvironment

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