ArticleNeuro-oncology2022
A comprehensive profiling of the immune microenvironment of breast cancer brain metastases.
Article in Neuro-oncology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 30 citations in OpenAlex.
- Phase 2 trial of perioperative chemo-immunotherapy for gastro-esophageal adenocarcinoma: The role of M2 macrophage landscape in predicting response.Cell reports. Medicine · 2025Trial
- The immunology of human breast cancer.Nature reviews. Immunology · 2026Review
- Article
- Brain metastasis-associated fibroblasts shape the tumour microenvironment to enhance cancer cell invasion.Brain pathology (Zurich, Switzerland) · 2026Article
- Future directions in the treatment of brain metastases: evaluating the role of cellular players in the tumour microenvironment.Acta neuropathologica · 2026Review
- Risk factors and metastatic sites in HER2-positive breast cancer with pathological complete response.NPJ breast cancer · 2026Article
- Characterization, immune cell phenotyping and differential gene expression analysis of brain metastases and primary breast cancer samples.Scientific reports · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- PD-1 inhibitor combined with chemoradiotherapy in two cases of ovarian cancer brain metastases: a case report.Frontiers in oncology · 2026Article
- Decoding the tumor microenvironment of triple-negative breast cancer: from immune evasion to precision immunotherapy.Frontiers in immunology · 2026Review
- SPP1+ macrophages polarized by lactate confer the progression of hypoxic adaptive tumor cells in brain.Neuro-oncology · 2026Article
- Cancer cell-monocyte co-culture spheroids recapitulate pro-tumorigenic, immunosuppressive, and drug-resistant microenvironments in brain metastatic breast cancer.NPJ breast cancer · 2025Article
- STAT3 expression in brain metastases from breast cancer is correlated with molecular subtype and impacts clinical outcome.Neuro-oncology · 2025Article
- The epigenetic landscape of brain metastasis.Oncogene · 2025Review
- Heterogeneous tissue-specific macrophages orchestrate metastatic organotropism of breast cancer: implications for promising therapeutics.Journal of translational medicine · 2025Review
- Genomic and immune profiling of breast cancer brain metastases.Acta neuropathologica communications · 2025Article
- A new, immunocompetent brain-metastatic mouse model of HER2-positive breast cancer.Clinical & experimental metastasis · 2025Article
- Highlighting recent achievements to advance more effective cancer immunotherapy.Journal of experimental & clinical cancer research : CR · 2025Article
- Divergent Crosstalk Between Microglia and T Cells in Brain Cancers: Implications for Novel Therapeutic Strategies.Biomedicines · 2025Review
- The immune landscape in brain metastasis.Neuro-oncology · 2025Review
Corrections and comments
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Authors and funding
17 authors at 6 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundDespite potential clinical implications, the complexity of breast cancer (BC) brain metastases (BM) immune microenvironment is poorly understood. Through multiplex immunofluorescence, we here describe the main features of BCBM immune microenvironment (density and spatial distribution) and evaluate its prognostic impact.
methodsSixty BCBM from patients undergoing neurosurgery at three institutions (2003-2018) were comprehensively assessed using two multiplex immunofluorescence panels (CD4, CD8, Granzyme B, FoxP3, CD68, pan-cytokeratin, DAPI; CD3, PD-1, PD-L1, LAG-3, TIM-3, CD163, pan-cytokeratin, DAPI). The prognostic impact of immune subpopulations and cell-to-cell spatial interactions was evaluated.
resultsSubtype-related differences in BCBM immune microenvironment and its prognostic impact were observed. While in HR-/HER2- BM and HER2+ BM, higher densities of intra-tumoral CD8+ lymphocytes were associated with significantly longer OS (HR 0.16 and 0.20, respectively), in HR+/HER2- BCBMs a higher CD4+FoxP3+/CD8+ cell ratio in the stroma was associated with worse OS (HR 5.4). Moreover, a higher density of intra-tumoral CD163+ M2-polarized microglia/macrophages in BCBMs was significantly associated with worse OS in HR-/HER2- and HR+/HER2- BCBMs (HR 6.56 and 4.68, respectively), but not in HER2+ BCBMs. In HER2+ BCBMs, multiplex immunofluorescence highlighted a negative prognostic role of PD-1/PD-L1 interaction: patients with a higher percentage of PD-L1+ cells spatially interacting with (within a 20 µm radius) PD-1+ cells presented a significantly worse OS (HR 4.60).
conclusionsOur results highlight subtype-related differences in BCBM immune microenvironment and identify two potential therapeutic targets, M2 microglia/macrophage polarization in HER2- and PD-1/PD-L1 interaction in HER2+ BCBMs, which warrant future exploration in clinical trials.
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