Dissecting the cellular architecture of breast cancer brain metastases reveals prognostically distinct immune landscapes
Menée à partir de l'analyse d'échantillons sanguins et d'échantillons tissulaires prélevés sur des patientes présentant des métastases cérébrales ayant pour origine un cancer du sein, cette étude met en évidence l'architecture cellulaire des métastases puis identifie deux profils immunitaires distincts (l'un caractérisé par des lymphocytes T mémoires résidents, l'autre par la présence de structures lymphoïdes tertiaires) qui permettent de prédire la survie des patients et leur réponse à l'immunothérapie
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.
Cancer Cell , article en libre accès, 2026