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T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels

To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cell...

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Main Authors: Messmer, Julia M. (Author) , Thommek, Calvin (Author) , Piechutta, Manuel (Author) , Venkataramani, Varun (Author) , Wehner, Rebekka (Author) , Westphal, Dana (Author) , Schubert, Marc Cicero (Author) , Mayer, Chanté D. (Author) , Effern, Maike (Author) , Berghoff, Anna S. (Author) , Hinze, Daniel (Author) , Helfrich, Iris (Author) , Schadendorf, Dirk (Author) , Wick, Wolfgang (Author) , Hölzel, Michael (Author) , Karreman, Matthia A. (Author) , Winkler, Frank (Author)
Format: Article (Journal)
Language:English
Published: 12 November 2024
In: Immunity
Year: 2024, Volume: 57, Issue: 11, Pages: 1-28
ISSN:1097-4180
DOI:10.1016/j.immuni.2024.09.003
Online Access:Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1016/j.immuni.2024.09.003
Verlag, lizenzpflichtig, Volltext: https://www.sciencedirect.com/science/article/pii/S1074761324004473
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Author Notes:Julia M. Messmer, Calvin Thommek, Manuel Piechutta, Varun Venkataramani, Rebekka Wehner, Dana Westphal, Marc Schubert, Chanté D. Mayer, Maike Effern, Anna S. Berghoff, Daniel Hinze, Iris Helfrich, Dirk Schadendorf, Wolfgang Wick, Michael Hölzel, Matthia A. Karreman, Frank Winkler
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Summary:To improve immunotherapy for brain tumors, it is important to determine the principal intracranial site of T cell recruitment from the bloodstream and their intracranial route to brain tumors. Using intravital microscopy in mouse models of intracranial melanoma, we discovered that circulating T cells preferably adhered and extravasated at a distinct type of venous blood vessel in the tumor vicinity, peritumoral venous vessels (PVVs). Other vascular structures were excluded as alternative T cell routes to intracranial melanomas. Anti-PD-1/CTLA-4 immune checkpoint inhibitors increased intracranial T cell motility, facilitating migration from PVVs to the tumor and subsequently inhibiting intracranial tumor growth. The endothelial adhesion molecule ICAM-1 was particularly expressed on PVVs, and, in samples of human brain metastases, ICAM-1 positivity of PVV-like vessels correlated with intratumoral T cell infiltration. These findings uncover a distinct mechanism by which the immune system can access and control brain tumors and potentially influence other brain pathologies.
Item Description:Gesehen am 19.09.2025
Physical Description:Online Resource
ISSN:1097-4180
DOI:10.1016/j.immuni.2024.09.003

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