ArticleESMO open2022
Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression.
Article in ESMO open, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
- Intrathecal Allogeneic B7-H3-Targeted CAR γδ T Cells for Leptomeningeal Metastasis from Solid Tumors: Safety, Efficacy, and Immunologic Dynamics in a Phase I Trial.Clinical cancer research : an official journal of the American Association for Cancer Research · 2026Article
- L-arginine metabolism in breast cancer: mechanisms and therapeutic targets.Frontiers in oncology · 2026Review
- Crosstalk in the brain tumor microenvironment: mechanisms, therapeutic strategies, and clinical advances.Military Medical Research · 2026Review
- Regulatory T cells in the breast cancer tumor microenvironment: new mechanisms, potential therapeutic strategies and future perspectives.American journal of cancer research · 2026Review
- Article
- TIGIT, as a potential immune checkpoint target for immunotherapy of breast cancer.Medical oncology (Northwood, London, England) · 2025Review
- Decoding tumor-infiltrating lymphocytes heterogeneity in ductal carcinoma in situ: immune microenvironment dynamics and prognostic insights.Discover oncology · 2025Review
- Genomic and immune profiling of breast cancer brain metastases.Acta neuropathologica communications · 2025Article
- Biological profile of breast cancer brain metastasis.Acta neuropathologica communications · 2025Review
- L-arginine dependence of breast cancer - molecular subtypes matter.BMC cancer · 2025Article
- Arginase Activity Inhibition With Thymoquinone Induces a Hybrid Type of Cell-Death in MDA-MB-231 Cell Line.Journal of biochemical and molecular toxicology · 2025Article
- Progress in personalized immunotherapy for patients with brain metastasis.NPJ precision oncology · 2025Review
- Review
- Analysis of neuroglia and immune cells in the tumor microenvironment of breast cancer brain metastasis.Cancer biology & therapy · 2024Review
- Breast cancer brain metastases genomic profiling identifies alterations targetable by immune-checkpoint and PARP inhibitors.NPJ precision oncology · 2024Article
- Review
- Immunotherapy in patients with brain metastasis: advances and challenges for the treatment and the application of circulating biomarkers.Frontiers in immunology · 2023Review
- The progress of microenvironment-targeted therapies in brain metastases.Frontiers in molecular biosciences · 2023Review
Corrections and comments
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Authors and funding
9 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundImmune checkpoint inhibition is an established treatment in programmed death-ligand 1 (PD-L1)-positive metastatic triple-negative (TN) breast cancer (BC). However, the immune landscape of breast cancer brain metastasis (BCBM) remains poorly defined. MATERIALS AND
methodsThe tumour-infiltrating lymphocytes (TILs) and the messenger RNA (mRNA) levels of 770 immune-related genes (NanoString™, nCounter™ Immuno-oncology IO360) were assessed in primary BCs and BCBMs. The prognostic role of ARG2 transcripts and protein expression in primary BCs and its association with outcome was determined.
resultsThere was a significant reduction of TILs in the BCBMs in comparison to primary BCs. 11.5% of BCs presented a high immune infiltrate (hot), 46.2% were altered (immunosuppressed/excluded) and 34.6% were cold (no/low immune infiltrate). 3.8% of BCBMs were hot, 23.1% altered and 73.1% cold. One hundred and twelve immune-related genes including PD-L1 and CTLA4 were decreased in BCBM compared to the primary BCs (false discovery rate <0.01, log2 fold-change >1.5). These genes are involved in matrix remodelling and metastasis, cytokine-chemokine signalling, lymphoid compartment, antigen presentation and immune cell adhesion and migration. Immuno-modulators such as PD-L1 (CD274), CTLA4, TIGIT and CD276 (B7H3) were decreased in BCBMs. However, PD-L1 and CTLA4 expression was significantly higher in TN BCBMs (P = 0.01), with CTLA4 expression also high in human epidermal growth factor receptor 2-positive (P < 0.01) compared to estrogen receptor-positive BCBMs. ARG2 was one of four genes up-regulated in BCBMs. High ARG2 mRNA expression in primary BCs was associated with worse distant metastasis-free survival (P = 0.038), while ARG2 protein expression was associated with worse breast-brain metastasis-free (P = 0.027) and overall survival (P = 0.019). High transcript levels of ARG2 correlated to low levels of cytotoxic and T cells in both BC and BCBM (P < 0.01).
conclusionThis study highlights the immunological differences between primary BCs and BCBMs and the potential importance of ARG2 expression in T-cell depletion and clinical outcome.
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