Immune Profiling of Combined Hepatocellular- Cholangiocarcinoma Reveals Distinct Subtypes and Activation of Gene Signatures Predictive of Response to Immunotherapy
| Autor: | Daniele Sommacale, Fouad Lafdil, Olivier Scatton, Hong Son Trinh, Thi Lan Tran, Christophe Tournigand, David Gentien, Isabelle Brocheriou, Van To Ta, Cong Trung Nguyen, Giuliana Amaddeo, Jean-Charles Nault, Luca Di Tommaso, Van Ky Le, Camille Boulagnon-Rombi, Stefano Caruso, Jessica Zucman-Rossi, Patrick Soussan, Manon Allaire, Jérémy Augustin, Hélène Regnault, Alain Luciani, Aurélie Beaufrère, Julien Calderaro, Valérie Paradis, Sébastien Mulé, Vincent Leroy, Frédéric Charlotte, Audrey Rapinat, Pascale Maillé, Anaïs Pujals, Raffaele Brustia, Alexis Laurent, Rami Rhaiem, Loëtitia Favre, Jean-Michel Pawlotsky |
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| Rok vydání: | 2021 |
| Předmět: |
Adult
Male Cancer Research Carcinoma Hepatocellular medicine.medical_treatment Antigen presentation Inflammation Malignancy Subclass Cholangiocarcinoma Neoplasms Multiple Primary Immune system medicine Humans Aged Aged 80 and over Innate immune system business.industry Liver Neoplasms Immunotherapy Middle Aged medicine.disease Treatment Outcome Oncology Bile Duct Neoplasms Cancer research Immunohistochemistry Female medicine.symptom business Forecasting |
| Zdroj: | Clinical cancer research : an official journal of the American Association for Cancer Research. 28(3) |
| ISSN: | 1557-3265 |
| Popis: | Purpose: 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. Experimental Design: 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. Results: 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. Conclusions: 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. |
| Databáze: | OpenAIRE |
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