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.
Overview
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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]
Citations
Cites
Molecular portraits of human breast tumours
Perou, C., Sørlie, T., Eisen, M., van de Rijn, M., Jeffrey, S., Rees, C. A., Pollack, J., Ross, D., Johnsen, H., Akslen, L., et al. (2000) · Nature · doi:10.1038/35021093 · Cited by 16,551
The blockade of immune checkpoints in cancer immunotherapy
Pardoll, D. M. (2012) · Nature Reviews Cancer · doi:10.1038/nrc3239 · Cited by 13,838
Sørlie, T., Perou, C. M., Tibshirani, R. J., Aas, T., Geisler, S. B., Johnsen, H., Hastie, T. J., Eisen, M. B., van de Rijn, M., Jeffrey, S. S., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.191367098 · Cited by 11,506
Freeman, G. J., Long, A. J., Iwai, Y., Bourque, K., Chernova, T., Nishimura, H., Fitz, L. J., Malenkovich, N., Okazaki, T., Byrne, M. C., et al. (2000) · The Journal of Experimental Medicine · doi:10.1084/jem.192.7.1027 · Cited by 5,294
Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538
Spatiotemporal Dynamics of Intratumoral Immune Cells Reveal the Immune Landscape in Human Cancer
Bindea, G., Mlecnik, B., Tosolini, M., Kirilovsky, A., Waldner, M. J., Obenauf, A. C., Angell, H. K., Fredriksen, T., Lafontaine, L., Berger, A., et al. (2013) · Immunity · doi:10.1016/j.immuni.2013.10.003 · Cited by 4,455
Orimo, A., Gupta, P. B., Sgroi, D. C., Arenzana-Seisdedos, F., Delaunay, T., Naeem, R., Carey, V. J., Richardson, A. L., & Weinberg, R. A. (2005) · Cell · doi:10.1016/j.cell.2005.02.034 · Cited by 3,759
PD-L2 is a second ligand for PD-1 and inhibits T cell activation
Latchman, Y., Wood, C. R., Chernova, T., Chaudhary, D., Borde, M., Chernova, I., Iwai, Y., Long, A. J., Brown, J. A., Nunes, R., et al. (2001) · Nature Immunology · doi:10.1038/85330 · Cited by 2,955
Mechanism-driven biomarkers to guide immune checkpoint blockade in cancer therapy
Topalian, S. L., Taube, J. M., Anders, R. A., & Pardoll, D. M. (2016) · Nature Reviews Cancer · doi:10.1038/nrc.2016.36 · Cited by 2,733
Özdemir, B. C., Pentcheva-Hoang, T., Carstens, J. L., Zheng, X., Wu, C.-C., Simpson, T. R., Laklai, H., Sugimoto, H., Kahlert, C., Novitskiy, S. V., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.005 · Cited by 2,681
Flagged first, then by citations
5 of the 74 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth
de Visser, K. E., & Joyce, J. A. (2023) · Cancer Cell · doi:10.1016/j.ccell.2023.02.016 · Cited by 4,059
A framework for advancing our understanding of cancer-associated fibroblasts
Sahai, E., Astsaturov, I., Cukierman, E., DeNardo, D. G., Egeblad, M., Evans, R. M., Fearon, D., Greten, F. R., Hingorani, S. R., Hunter, T., et al. (2020) · Nature Reviews Cancer · doi:10.1038/s41568-019-0238-1 · Cited by 3,863
Macrophages as regulators of tumour immunity and immunotherapy
DeNardo, D. G., & Ruffell, B. (2019) · Nature reviews. Immunology · doi:10.1038/s41577-019-0127-6 · Cited by 2,591
Mao, X., Xu, J., Wang, W., Liang, C., Hua, J., Liu, J., Zhang, B., Meng, Q., Yu, X., & Shi, S. (2021) · Molecular Cancer · doi:10.1186/s12943-021-01428-1 · Cited by 2,290
“Breast cancer CAF-S1 CD29, FAP, α-SMA, PDGFRβ, FSP1 and CXCL12 Tumor proliferation, Migration, Lymph-nodes metastasis, Immune suppression and EMT initiation [96, 98]”
BackgroundInfluentialElyada, E., Bolisetty, M., Laise, P., Flynn, W. F., Courtois, E. T., Burkhart, R. A., Teinor, J. A., Belleau, P., Biffi, G., Lucito, M. S., et al. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-19-0094 · Cited by 2,241
“The role of Tregs in inhibiting immune responses in cancer has long been established (39, 40), and mechanisms of Treg infiltration have been described in PDAC as well (41–43).”
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
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
