{"entity": "publication", "iuid": "5bb8ae8f6ba84927ace55253c2cc8ae1", "timestamp": "2026-08-21T22:26:49.252Z", "links": {"self": {"href": "https://publications-affiliated.scilifelab.se/publication/5bb8ae8f6ba84927ace55253c2cc8ae1.json"}, "display": {"href": "https://publications-affiliated.scilifelab.se/publication/5bb8ae8f6ba84927ace55253c2cc8ae1"}}, "title": "Tumor endothelial cell up-regulation of IDO1 is an immunosuppressive feed-back mechanism that reduces the response to CD40-stimulating immunotherapy.", "authors": [{"family": "Georganaki", "given": "Maria", "initials": "M"}, {"family": "Ramachandran", "given": "Mohanraj", "initials": "M"}, {"family": "Tuit", "given": "Sander", "initials": "S"}, {"family": "N\u00fa\u00f1ez", "given": "Nicol\u00e1s Gonzalo", "initials": "NG"}, {"family": "Karampatzakis", "given": "Alexandros", "initials": "A"}, {"family": "Fotaki", "given": "Grammatiki", "initials": "G"}, {"family": "van Hooren", "given": "Luuk", "initials": "L"}, {"family": "Huang", "given": "Hua", "initials": "H"}, {"family": "Lugano", "given": "Roberta", "initials": "R"}, {"family": "Ulas", "given": "Thomas", "initials": "T", "orcid": "0000-0002-9785-4197", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/1fe5950df6e141b7aab952703e0c0c46.json"}}, {"family": "Kaunisto", "given": "Aura", "initials": "A"}, {"family": "Holland", "given": "Eric C", "initials": "EC"}, {"family": "Ellmark", "given": "Peter", "initials": "P"}, {"family": "Mangsbo", "given": "Sara M", "initials": "SM"}, {"family": "Schultze", "given": "Joachim", "initials": "J"}, {"family": "Essand", "given": "Magnus", "initials": "M"}, {"family": "Tugues", "given": "Sonia", "initials": "S"}, {"family": "Dimberg", "given": "Anna", "initials": "A", "orcid": "0000-0003-4422-9125", "researcher": {"href": "https://publications-affiliated.scilifelab.se/researcher/6f5d91c4b8784d8081a41604bb3d78d4.json"}}], "type": "journal article", "published": "2020-03-09", "journal": {"title": "Oncoimmunology", "issn": "2162-4011", "volume": "9", "issue": "1", "pages": "1730538", "issn-l": null}, "abstract": "CD40-stimulating immunotherapy can elicit potent anti-tumor responses by activating dendritic cells and enhancing T-cell priming. Tumor vessels orchestrate T-cell recruitment during immune response, but the effect of CD40-stimulating immunotherapy on tumor endothelial cells has not been evaluated. Here, we have investigated how tumor endothelial cells transcriptionally respond to CD40-stimulating immunotherapy by isolating tumor endothelial cells from agonistic CD40 mAb- or isotype-treated mice bearing B16-F10 melanoma, and performing RNA-sequencing. Gene set enrichment analysis revealed that agonistic CD40 mAb therapy increased interferon (IFN)-related responses in tumor endothelial cells, including up-regulation of the immunosuppressive enzyme Indoleamine 2, 3-Dioxygenase 1 (IDO1). IDO1 was predominantly expressed in endothelial cells within the tumor microenvironment, and its expression in tumor endothelium was positively correlated to T-cell infiltration and to increased intratumoral expression of IFN\u03b3. In vitro, endothelial cells up-regulated IDO1 in response to T-cell-derived IFN\u03b3, but not in response to CD40-stimulation. Combining agonistic CD40 mAb therapy with the IDO1 inhibitor epacadostat delayed tumor growth in B16-F10 melanoma, associated with increased activation of tumor-infiltrating T-cells. Hereby, we show that the tumor endothelial cells up-regulate IDO1 upon CD40-stimulating immunotherapy in response to increased IFN\u03b3-secretion by T-cells, revealing a novel immunosuppressive feedback mechanism whereby tumor vessels limit T-cell activation.", "doi": "10.1080/2162402X.2020.1730538", "pmid": "32231867", "labels": [], "xrefs": [{"db": "pmc", "key": "PMC7094447"}, {"db": "pii", "key": "1730538"}], "notes": [], "created": "2026-08-20T09:37:30.762Z", "modified": "2026-08-21T09:28:20.269Z"}