MassIVE MSV000100316

Partial Public PXD072349

MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumour growth

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Description

Cholangiocarcinoma (CCA) comprises a heterogeneous group of biliary malignant tumours with poor prognosis. Recent studies highlight the immune systems role in the development and progression of intrahepatic CCA (iCCA). In this study, we investigated the role of the scavenger receptor MARCO in iCCA. MARCO was found on a specific subtype of tumour-associated macrophages and linked to immunosuppression and extracellular matrix remodelling in iCCA. High MARCO expression in human iCCA tumours correlated with worse overall survival, T cell dysfunction and increased collagen depositition. Marco-/- mice were protected against iCCA development, with fewer innate immune cells related to TH2 responses and less fibrosis. Moreover, Marco-/- mice exhibited lower levels of immunosuppressive markers on macrophages and cytotoxic T cells, resulting in better survival and fewer lung metastases. The use of an anti-MARCO antibody further reduced tumour volume in wild-type mice. This study identifies MARCO as a new therapeutic target in iCCA. [doi:10.25345/C5PK07F66] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: tumour immunology ; oncology ; biliary cancer ; immunotherapy ; macrophages ; innate immunity ; DatasetType:Proteomics

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Principal Investigators:
(in alphabetical order) 		Jesus Maria Banales, Biogipuzkoa HRI, Spain
Maria Jesis Perugorria, Facultad de Medicina y Enfermeria. UPV-EHU, Spain
Submitting User: ibonil
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