ArticleFrontiers in immunology2022
3D Collagen Fiber Concentration Regulates Treg Cell Infiltration in Triple Negative Breast Cancer.
Article in Frontiers in immunology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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16 citing papers in PubMed, 18 citations in OpenAlex.
- LOXL4: a key regulatory factor at the intersection of fibrosis and tumor progression.Human cell · 2026Review
- The extracellular matrix in inflammation and cancer.Molecular biomedicine · 2026Review
- Regulatory T cells in the breast cancer tumor microenvironment: new mechanisms, potential therapeutic strategies and future perspectives.American journal of cancer research · 2026Review
- Tumor microenvironment-induced epigenetic reprogramming of Tregs and its impact on immunotherapy.Frontiers in genetics · 2026Review
- Collagen dynamics in the breast cancer tumor microenvironment and therapeutic perspectives.Discover oncology · 2025Review
- Biomechanics of the tumor extracellular matrix and regulatory T cells: regulatory mechanisms and potential therapeutic targets.Cell communication and signaling : CCS · 2025Review
- Interleukin-1β mediates a tumor-supporting environment prompted by IGF1 in triple-negative breast cancer (TNBC).Journal of translational medicine · 2025Article
- Review
- High levels of fibrotic tumor components are associated with recurrence and intratumoral immune status in advanced colorectal cancer patients.Scientific reports · 2024Article
- Patterns of immune evasion in triple-negative breast cancer and new potential therapeutic targets: a review.Frontiers in immunology · 2024Review
- Crosstalk between T lymphocyte and extracellular matrix in tumor microenvironment.Frontiers in immunology · 2024Review
- Targeting extracellular matrix stiffness for cancer therapy.Frontiers in immunology · 2024Review
- Article
- Association of collagen deep learning classifier with prognosis and chemotherapy benefits in stage II-III colon cancer.Bioengineering & translational medicine · 2023Article
- Review
- Review
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Background: Triple negative breast cancer (TNBC) is characterized by poor prognosis and a lack of effective therapeutic agents owing to the absence of biomarkers. A high abundance of tumor-infiltrating regulatory T cells (Tregs) was associated with worse prognosis in malignant disease. Exploring the association between Treg cell infiltration and TNBC will provide new insights for understanding TNBC immunosuppression and may pave the way for developing novel immune-based treatments. Materials and Methods: Patients from TCGA were divided into Treg-high (Treg-H) and Treg-low (Treg-L) groups based on the abundance of Tregs according to CIBERSORT analysis. The association between expression level of Tregs and the clinical characteristics as well as prognosis of breast cancer were evaluated. Next, a Treg-related prognostic model was established after survival-dependent univariate Cox and LASSO regression analysis, companied with an external GEO cohort validation. Then, GO, KEGG and GSEA analyses were performed between the Treg-H and Treg-L groups. Masson and Sirius red/Fast Green staining were applied for ECM characterization. Accordingly, Jurkat T cells were encapsulated in 3D collagen to mimic the ECM microenvironment, and the expression levels of CD4, FOXP3 and CD25 were quantified according to immunofluorescence staining. Results: The expression level of Tregs is significantly associated with the clinical characteristics of breast cancer patients, and a high level of Treg cell expression indicates a poor prognosis in TNBC. To further evaluate this, a Treg-related prognostic model was established that accurately predicted outcomes in both TCGA training and GEO validation cohorts of TNBC patients. Subsequently, ECM-associated signaling pathways were identified between the Treg-H and Treg-L groups, indicating the role of ECM in Treg infiltration. Since we found increasing collagen concentrations in TNBC patients with distant migration, we encapsulated Jurkat T cells within a 3D matrix with different collagen concentrations and observed that increasing collagen concentrations promoted the expression of Treg biomarkers, supporting the regulatory role of ECM in Treg infiltration. Conclusion: Our results support the association between Treg expression and breast cancer progression as well as prognosis in the TNBC subtype. Moreover, increasing collagen density may promote Treg infiltration, and thus induce an immunosuppressed TME.
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