Journal Article

DKFZ-2026-01015

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dissecting the cellular architecture of breast cancer brain metastases reveals prognostically distinct immune landscapes.

Jassowicz, L. (First author)DKFZ* ; Feng, F.DKFZ* ; Warta, R. ; Heinicke, F. ; Wöllner, A. ; Briesch, H.DKFZ* ; Sor, F. ; Soller, J. ; Lotsch, C. ; Wong, J. K. L.DKFZ* ; Park, C.DKFZ* ; Aubert, N.DKFZ* ; Scheer, M. ; Hu, Z.DKFZ* ; Knoll, M.DKFZ* ; Schlegel, J.DKFZ* ; Frank, L.DKFZ* ; Dao Trong, P. ; Jungwirth, G. ; Nohman, A. I. ; Maass, K.DKFZ* ; Grabe, N. ; Barthel, M. ; Butz, S. ; Lulay, C. ; Zucknick, M. ; Bortolomeazzi, M.DKFZ* ; Sant, P.DKFZ* ; Thewes, V.DKFZ* ; Michel, L. ; Fremd, C.DKFZ* ; Schneeweiss, A.DKFZ* ; Sun, C.DKFZ* ; Rippe, K.DKFZ* ; Abdollahi, A.DKFZ* ; von Deimling, A. ; Unterberg, A. ; Krieg, S. M. ; Mallm, J.-P.DKFZ* ; Lichter, P.DKFZ* ; Zapatka, M.DKFZ* ; Seiffert, M. (Last author)DKFZ* ; Herold-Mende, C.

2026
Cell Press Cambridge, Mass.

Abstract: Breast cancer brain metastases (BCBM) are a severe condition with high demand for improved personalized treatment, but a comprehensive understanding of BCBM immune-microenvironment heterogeneity and susceptibility to immunotherapy is lacking. Here, we multimodally profile the immune niche in a clinically well-annotated cohort of 156 BCBM applying tissue cytometry, bulk and single nuclei RNA-sequencing, flow cytometry, and spatial transcriptomics, complemented by functional studies in patient-derived models. Integrative analyses reveal two immune landscapes predicting prolonged patient survival and that are not deducible from paired primary tumors: 1) BCBM with a high proportion of CD8+ tissue-resident-like memory T cells as major players of tumor immune control. 2) BCBM containing tertiary lymphoid structures. Surrogate signatures of these landscapes are prognostic in independent BCBM and primary breast cancer cohorts, are associated with fewer metastases, and predict immunotherapy response. Our work provides critical insights into anti-tumor immunity in BCBM and identifies novel biomarkers with translational relevance.

Keyword(s): biomarkers ; brain metastases ; breast cancer ; immunotherapy ; single-cell analysis ; spatial neighborhood, tumor organoids ; tertiary lymphoid structures ; tissue-resident memory T cells ; tumor microenvironment

Note: #EA:B060#LA:B060# / #NCTZFB26# / epub

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Contributing Institute(s):

1. B060 Molekulare Genetik (B060)
2. NWG Krebs-Immunregulation (D250)
3. E210 KKE Translationale Radioonkologie (E210)
4. B066 Chromatin-Netzwerke (B066)
5. B062 Pädiatrische Neuroonkologie (B062)
6. Single-cell Open Lab (W192)
7. Koordinierungsstelle NCT Heidelberg (HD02)

Research Program(s):

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

Appears in the scientific report 2026

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; Current Contents - Life Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 50 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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