UEG's educational platform for gastroenterology education bringing recordings, courses, guidelines, and more together in one place.

UEG Week Berlin 2025 Recordings Gut Guide online

Rate for better recommendations!

Your feedback helps us show you more of what you like and less of what you dislike!

More of this!

We will show you more similar content.

Not for me!

We won't suggest this again.

Bookmark!

Save this content for later!

New to myUEG? Create an account! Log In with myUEG account

UEG Poster

Standard Poster

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

Not sure what you can access? Learn more about account types.

SCAVENGER RECEPTOR MARCO IS ASSOCIATED WITH AN IMMUNOSUPPRESSIVE MICROENVIRONMENT AND TUMOR PROGRESSION IN INTRAHEPATIC CHOLANGIOCARCINOMA

Aloña Agirre Lizaso 1, Maider Huici-Izagirre 1, Colm J. O'Rourke 2, Ekaterina Zhuravleva 2, Ana Korosec 3, Mikel Azkargorta 4, Felix Elortza 4, Sumera I. Ilyas 5, Gregory J. Gores 5, Jesper B. Andersen 2, Gernot Schabbauer 3, Luis Bujanda Fernández de Piérola 6, Pedro M. Rodrigues 7, Omar Sharif 3, Jesús M. Bañales 8, María Jesús Perugorria 9

Affiliations

1 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain

2 Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

3 Institute for Vascular Biology, Centre for Physiology and Pharmacology, Medical University Vienna, Christian Doppler Laboratory for Arginine Metabolism in Rheumatoid Arthritis and Multiple Sclerosis, Vienna, Austria

4 CIBERehd, Instituto de Salud Carlos III (ISCIII), Madrid, Spain|||Proteomics Platform, CIC bioGUNE, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain

5 Division of Gastroenterology and Hepatology, Mayo Clinic, Rochester, United States

6 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||CIBERehd, Instituto de Salud Carlos III (ISCIII), Madrid, Spain

7 CIBERehd, Instituto de Salud Carlos III (ISCIII), Madrid, Spain|||Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||IKERBASQUE, Basque Foundation for Science, Bilbao, Spain

8 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||CIBERehd, Instituto de Salud Carlos III (ISCIII), Madrid, Spain|||IKERBASQUE, Basque Foundation for Science, Bilbao, Spain|||University of Navarra, Pamplona,

9 Donostia University Hospital, University of the Basque Country (UPV/EHU), San Sebastian, Spain|||CIBERehd, Instituto de Salud Carlos III (ISCIII), Madrid, Spain|||Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain

Summary

AI Generated

High MARCO expression in intrahepatic cholangiocarcinoma is associated with worse patient outcomes and an immunosuppressive tumor microenvironment, and MARCO deficiency improves survival in murine models by reducing immunosuppressive cell populations and metastasis.

High MARCO expression levels in liver samples of patients with intrahepatic cholangiocarcinoma are linked with worse clinical outcome and associated with M2 macrophages and T cell dysfunction.
MARCO-deficient mice show a trend toward protection from intrahepatic cholangiocarcinoma development, with reduction in CD9+Ly6C-F4/80+ resident macrophages and type-2 innate lymphoid cells.
In orthotopic models, MARCO-deficient mice exhibit reduced immune checkpoint molecules including lower percentages of PD-L1+ resident macrophages and PD-1+ and CTLA-4+ cytotoxic CD8+ T cells compared to wild-type mice.
MARCO deficiency significantly improves overall survival in mice with orthotopic syngeneic cholangiocarcinoma due to reduced tumor metastasis in the lungs.
The findings suggest MARCO as a novel therapeutic target for intrahepatic cholangiocarcinoma.

Download PDF

Was this helpful?

Thanks for your feedback.

This summary was generated by an AI large language model based on the content transcript. It is for informational purposes only and should not be considered a substitute for clinical judgment. Always rely on your professional expertise and the full clinical context when making clinical decisions.

Abstract

Introduction

Cholangiocarcinoma (CCA) comprises a heterogeneous group of malignant tumours with dismal prognosis. During the last years, different studies have highlighted the key role of the immune system in the development of intrahepatic CCA (iCCA) and several combinational therapies targeting the tumour microenvironment (TME) have shown promising results for anti-cancer therapy. In this regard, the macrophage receptor with collagenous structure (MARCO) is a class A scavenger receptor found on particular subsets of macrophages that has been described to play a determining role in macrophage polarization and consequently in adaptive immune responses in many solid tumours. However, its role in iCCA is still unknown. This study aims to unravel the role of MARCO in iCCA development and progression.

Aims & Methods

The cell-type specific MARCO expression was examined in iCCA human tumors by using publicly available single-cell RNA sequencing data from different studies and MARCO-expressing tumor-associated macrophages (TAMs) were phenotypically characterized. MARCO mRNA expression was analyzed in human control and iCCA liver tissue samples and associated to different immune cell types and immune-functionality scores employing state-of-the-art technologies as ConsensusTME, Tumour Immune Dysfunction and Exclusion (TIDE) tool and Tumour Immunophenotype Profiling (TIP). To study the role of MARCO in murine cholangiocarcinogenesis, wild type (WT) and Marco^-/- mice were subjected to 3 different iCCA murine models and flow cytometry analysis of the TME was carried out to characterize different lymphocytic and myeloid populations.

Results

Single-cell RNA sequencing data indicate that MARCO is expressed in a specific subtype of TAMs in patients with iCCA. Besides, high MARCO expression levels in the liver samples of patients with iCCA are linked with worse clinical outcome. In line with this, MARCO expression in human iCCA tumours is associated to cell types involved in tumour progression such as M2 macrophages, and related with T cell dysfunction. Regarding the potential role of MARCO in murine models of iCCA, Marco^-/- mice show a trend to be protected from iCCA development, the mechanisms behind this effect being likely associated to a reduction of the innate immune cells such as CD9⁺Ly6C^-F4/80⁺ resident macrophages and type-2 innate lymphoid cells (ILC2). Noteworthy, in a context of a syngeneic orthotopic experimental model, Marco^-/- mice exhibit a reduced presence of immune checkpoint molecules in innate and adaptive immune cells, including a lower percentage of PD-L1⁺Ly6C^-F4/80⁺ resident macrophages and, PD-1⁺ and CTLA-4⁺ cytotoxic CD8⁺ T cells in comparison to WT mice. In addition, MARCO deficiency significantly improves the overall survival of mice subjected to the orthotopic injection of syngeneic CCA cells into the liver, due to a reduction of the tumour metastasis in the lungs.

Conclusion

High MARCO expression is associated to a worse outcome in patients with iCCA and is associated to an immunosuppressive TME. Importantly, Marco^-/- mice display a reduced presence of immunosuppressive cell populations and present an increased overall survival. Therefore, MARCO arises as a novel therapeutic target for iCCA.

Conference

UEG Week Copenhagen 2023

Topics

Hepatobiliary

Submission format

Abstract

Session

Oncology, transplantation and encephalopathy (Posters)

Citation

United European Gastroenterology Journal 2023; 11 (Supplement 8)

Published

2023

More Like This:

THERAPEUTIC POTENTIAL OF TARGETING PROTEIN HYPER-SUMOYLATION IN CHOLANGIOCARCINOMA

Maria L. Martinez-Chantar

DISSECTING THE HINDRANCE OF HEDGEHOG PATHWAY IN INTRAHEPATIC CHOLANGIOCARCINOMA: A STEP TOWARDS TARGETED THERAPY

Guido Carpino

EASL-ILCA Clinical Practice Guidelines on the management of intrahepatic cholangiocarcinoma

KLF5 UPREGULATION IS A COMMON EVENT IN CHOLANGIOCARCINOMA, ACTING AS AN ONCOGENE AND CONSTITUTING A BAD PROGNOSTIC FACTOR

Jesper B. Andersen

NOVEL PLATINUM-BASED CHEMOTHERAPEUTIC AGENTS HALT CHOLANGIOCARCINOMA PROGRESSION THROUGH THE INDUCTION OF DOUBLE-STRAND DNA BREAKS, PREVENTING DNA REPAIR MECHANISMS

Paula Olaizola

IMMUNO-ONCOLOGY BIOMARKERS FOR IMPROVED DIAGNOSIS OF CHOLANGIOCARCINOMA IN PRIMARY SCLEROSING CHOLANGITIS: INSIGHTS FROM THE INFLAMMATORY AND FIBROTIC TUMOUR MICROENVIRONMENT

Pilar Acedo

UEG Poster

Standard Poster

Share via Email Share on Facebook Share on X Share on LinkedIn Share on Bluesky

This content is part of Gutflix. Log in with your myUEG account, or create one free, to watch it.

Not sure what you can access? Learn more about account types.

THERAPEUTIC POTENTIAL OF TARGETING PROTEIN HYPER-SUMOYLATION IN CHOLANGIOCARCINOMA

Paula Olaizola 1, Irene Olaizola 2, Marta Fernandez de Ara 2, Maite G. Fernandez-Barrena 3, Laura Alvarez 4, Mikel Azkargorta 5, Colm J. O'Rourke 6, Pui-Yuen Lee-Law 7, Luiz M. Nova-Camacho 8, Jose Juan Marin 9, Maria L. Martinez-Chantar 10, Matias A. Avila 3, Patricia Aspichueta 11, Felix Elortza 5, Jesper B. Andersen 6, Luis Bujanda Fernández de Piérola 1, Pedro M. Rodrigues 12, María Jesús Perugorria 13, Jesús M. Bañales 12

Affiliations

1 Biodonostia Health Research Institute - Donostia University Hospital, San Sebastian, Spain|||National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain

2 Biodonostia Health Research Institute - Donostia University Hospital, San Sebastian, Spain

3 National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||Hepatology Program, CIMA, University of Navarra, Pamplona, Spain|||Instituto de Investigaciones Sanitarias de Navarra (Idi

4 Hepatology Program, CIMA, University of Navarra, Pamplona, Spain

5 National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||Proteomics Platform, CIC bioGUNE, CIBERehd, ProteoRed-ISCIII, Bizkaia Science and Technology Park, Derio, Spain

6 Biotech Research and Innovation Centre (BRIC), Department of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark

7 Biodonostia Health Research Institute - Donostia University Hospital, San Sebastian, Spain|||Radboud University Nijmegen Medical Center, Nijmegen, Netherlands

8 Osakidetza Basque Health Service, Donostialdea IHO, Donostia University Hospital, Department of Pathology, San Sebastian, Spain

9 National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||Experimental Hepatology and Drug Targeting (HEVEPHARM) Group, Institute of Biomedical Research of Salamanca (IBSAL), Unive

10 National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||Liver Disease Laboratory, CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Bilbao, Spain

11 National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||Faculty of Medicine and Nursing, University of the Basque Country (UPV/EHU), Leioa, Spain|||Biocruces Bizkaia Health Resea

12 Biodonostia Health Research Institute - Donostia University Hospital, San Sebastian, Spain|||National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||IKERBASQUE, Basque Foundation

13 Biodonostia Health Research Institute - Donostia University Hospital, San Sebastian, Spain|||National Institute for the Study of Liver and Gastrointestinal Diseases (CIBERehd, “Instituto de Salud Carlos III”), Madrid, Spain|||Faculty of Medicine and Nursi