MARCO promotes cholangiocarcinogenesis by inducing immunosuppression and its targeting reduces tumour growth
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ABSTRACT: 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.
INSTRUMENT(S): timsTOF Pro
ORGANISM(S): Mus Musculus (ncbitaxon:10090)
SUBMITTER:
Jesus Maria Banales
Maria Jesis Perugorria
PROVIDER: MSV000100316 | MassIVE | Tue Dec 23 05:38:00 GMT 2025
SECONDARY ACCESSION(S): PXD072349
REPOSITORIES: MassIVE
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