Journal Article

DKFZ-2024-02003

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png T lymphocyte recruitment to melanoma brain tumors depends on distinct venous vessels.

Messmer, J. (First author)DKFZ* ; Thommek, C.DKFZ* ; Piechutta, M.DKFZ* ; Venkataramani, V. ; Wehner, R.DKFZ* ; Westphal, D. ; Schubert, M. ; Mayer, C. D.DKFZ* ; Effern, M. ; Berghoff, A. S. ; Hinze, D. ; Helfrich, I.DKFZ* ; Schadendorf, D. ; Wick, W.DKFZ* ; Hölzel, M. ; Karreman, M. A. (Last author)DKFZ* ; Winkler, F. (Last author)DKFZ*

2024
Elsevier New York, NY

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Please use a persistent id in citations: doi:10.1016/j.immuni.2024.09.003

Abstract: 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.

Keyword(s): brain cancer ; brain metastases ; brain metastasis ; cancer ; immunotherapy ; intravital imaging ; lymphocyte recruitment ; melanoma ; tumor immunology

Note: #EA:B320#LA:B320# / Volume 57, Issue 11, 12 November 2024, Pages 2688-2703.e11

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Contributing Institute(s):

1. KKE Neuroonkologie (B320)
2. DKTK HD zentral (HD01)
3. DKTK Koordinierungsstelle Dresden (DD01)
4. DKTK Koordinierungsstelle München (MU01)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2024

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Database coverage:
; ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 30 ; JCR ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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