Journal Article

DKFZ-2023-00355

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Endothelial Indoleamine-2,3-Dioxygenase-1 is not Critically Involved in Regulating Antitumor Immunity in the Central Nervous System

Abu Hejleh, A. (First author)DKFZ* ; Huck, K.DKFZ* ; Jähne, K.DKFZ* ; Tan, C.DKFZ* ; Lanz, T. ; Epping, L. ; Sonner, J. ; Meuth, S. ; Henneberg, A.DKFZ* ; Opitz, C.DKFZ* ; Herold-Mende, C. ; Sahm, F.DKFZ* ; Platten, M.DKFZ* ; Sahm, K. (Last author)DKFZ*

2023
Sage Publications Thousand Oaks, CA

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Please use a persistent id in citations: doi:10.1177/11786469231153111

Abstract: The vascular niche of malignant gliomas is a key compartment that shapes the immunosuppressive brain tumor microenvironment (TME). The blood-brain-barrier (BBB) consisting of specialized endothelial cells (ECs) and perivascular cells forms a tight anatomical and functional barrier critically controlling transmigration and effector function of immune cells. During neuroinflammation and tumor progression, the metabolism of the essential amino acid tryptophan (Trp) to metabolites such as kynurenine has long been identified as an important metabolic pathway suppressing immune responses. Previous studies have demonstrated that indoleamine-2,3-dioxygenase-1 (IDO1), a key rate-limiting enzyme in tryptophan catabolism, is expressed within the TME of high-grade gliomas. Here, we investigate the role of endothelial IDO1 (eIDO1) expression for brain tumor immunity. Single-cell RNA sequencing data revealed that in human glioma tissue, IDO1 is predominantly expressed by activated ECs showing a JAK/STAT signaling pathway-related CXCL11+ gene expression signature. In a syngeneic experimental glioma model, eIDO1 is induced by low-dose tumor irradiation. However, cell type-specific ablation of eIDO1 in experimental gliomas did not alter frequency and phenotype of tumor-infiltrating T cells nor tumor growth. Taken together these data argue against a dominant role of eIDO1 for brain tumor immunity.

Note: #EA:D170#LA:D170#

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Contributing Institute(s):

1. KKE Neuroimmunologie und Hirntumorimmunologie (D170)
2. DKTK HD zentral (HD01)
3. Metabolischer Crosstalk bei Krebserkrankungen (B350)
4. KKE Neuropathologie (B300)

Research Program(s):

1. 314 - Immunologie und Krebs (POF4-314) (POF4-314)

Appears in the scientific report 2023

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Database coverage:
; ; Article Processing Charges ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Emerging Sources Citation Index ; Fees ; IF < 5 ; JCR ; National-Konsortium ; PubMed Central ; SCOPUS ; Web of Science Core Collection

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