The DOI matches its Crossref record; 69 of the 74 references it cites were found in a registry or an index.
Fibroblast Heterogeneity and Immunosuppressive Environment in Human Breast Cancer
Open accessAbstract
Carcinoma-associated fibroblasts (CAF) are key players in the tumor microenvironment. Here, we characterize four CAF subsets in breast cancer with distinct properties and levels of activation. Two myofibroblastic subsets (CAF-S1, CAF-S4) accumulate differentially in triple-negative breast cancers (TNBC). CAF-S1 fibroblasts promote an immunosuppressive environment through a multi-step mechanism. By secreting CXCL12, CAF-S1 attracts CD4+CD25+ T lymphocytes and retains them by OX40L, PD-L2, and JAM2. Moreover, CAF-S1 increases T lymphocyte survival and promotes their differentiation into CD25 High FOXP3 High, through B7H3, CD73, and DPP4. Finally, in contrast to CAF-S4, CAF-S1 enhances the regulatory T cell capacity to inhibit T effector proliferation. These data are consistent with FOXP3+ T lymphocyte accumulation in CAF-S1-enriched TNBC and show how a CAF subset contributes to immunosuppression.
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In the citing paper
“Interestingly, CD276 (B7-H3), known to augment Tregs and inhibit T cell responses (Costa et al., 2018, Prasad et al., 2004, Suh et al., 2003), was expressed most prominently on CAFs and TSKs.”
From Multimodal Analysis of Composition and Spatial Architecture in Human Squamous Cell Carcinoma (2020) · cites this paper as Costa et al., 2018
In the citing paper
“FAP-high fibroblasts are correlated with Treg cell-mediated immunosuppression and a poor outcome119”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [119]
In the citing paper
“Clinical analysis further supports an inverse association between CAFs and CD8+ T cells119.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [119]
In the citing paper
“Breast cancer also shows divergent CAF phenotypes, with the primary discriminating marker being FAP.”
From A framework for advancing our understanding of cancer-associated fibroblasts (2020) · cites this paper as [119]
In the citing paper
“Additionally, they can help define the immunosuppressive environment, through effects on immune cell activation and impeding infiltration of immune cells into tumors227–231.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [227]
In the citing paper
“Stromal fibroblasts are a major source of TGF-β in the TME40,227.”
From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [227]
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BackgroundInfluential
Metadata
- Authors
- Costa, A., Kieffer, Y., Scholer-Dahirel, A., Pelon, F., Bourachot, B., Cardon, M., Sirven, P., Magagna, I., Fuhrmann, L., Bernard, C., Bonneau, C., Kondratova, M., Kuperstein, I., Zinovyev, A., Givel, A.-M., Parrini, M.-C., Soumelis, V., Vincent-Salomon, A., & Mechta-Grigoriou, F.
- Affiliations
- Inserm (FR)
- Institut Curie (FR)
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2018-03
- Volume
- 33
- Issue
- 3
- Pages
- 463-479.e10
- ISSN
- 1535-6108 (ISSN-L)
- OpenAlex
- W2786031287
- Cited by
- 1,705
- References
- 74
- Citations by year
- 2026: 165 · 2025: 202 · 2024: 264 · 2023: 255 · 2022: 236 · 2021: 262 · 2020: 173 · 2019: 99 · 2018: 47
- FWCI
- 54.69
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- HAL (submittedVersion)
- Funders
- Fondation de France
- Fondation Pierre-Gilles de Gennes
- Institut National Du Cancer (INCa-DGOS-9963)
- Fondation pour la Recherche Médicale
- SiRIC-Curie program (INCa-DGOS-4654)
- Institut National de la Santé et de la Recherche Médicale
- Institut Curie
- Ligue Nationale Contre le Cancer
- ICGex (ANR-10-EQPX-03)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
- Keywords
- cancer-associated fibroblasts, breast cancer, triple-negative breast cancer, tumor microenvironment, immunosuppression, regulatory T cells, CXCL12, OX40L, PD-L2, JAM2, B7-H3, CD73, dipeptidyl peptidase IV, Foxp3, CD4+ T cells, T cell survival, fibroblast heterogeneity
- MeSH terms
- Breast Neoplasms, Cell Differentiation, Fibroblasts, Humans, Immune Tolerance, Lymphocyte Activation, Lymphocytes, Tumor-Infiltrating, Cell Proliferation, T-Lymphocytes, Regulatory, Forkhead Transcription Factors, Tumor Microenvironment
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