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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“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
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Items 701–800 of 1,002
Senescent Fibroblasts Generate a CAF Phenotype through the Stat3 Pathway
Li, H., Qiu, L., Liu, Q., Ma, Z., Xie, X., Luo, Y., & Wu, X. (2022) · Genes · doi:10.3390/genes13091579 · Cited by 29
Stromal circuits involving tumor-associated macrophages and cancer-associated fibroblasts
Timperi, E., & Romano, E. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1194642 · Cited by 29
“CAF subsets have been described to modulate immune responses, inducing regulatory T cell programs, T cell suppressive activities and recruiting myeloid cells at the tumor site (38).”
BackgroundPeng, S., Hebert, L. L., Eschbacher, J. M., & Kim, S. (2020) · Cancers · doi:10.3390/cancers12123639 · Cited by 27
“More recently, carcinoma-associated fibroblasts (CAFs) have been delineated to four subgroups by large undertaking of mapping multiple cell markers using multicolor flow cytometry [38].”
BackgroundUnlocking antitumor immunity with adenosine receptor blockers
Remley, V. A., Linden, J. M., Bauer, T. W., & Dimastromatteo, J. (2023) · Cancer Drug Resistance · doi:10.20517/cdr.2023.63 · Cited by 27
Hazrati, A., Malekpour, K., Mirsanei, Z., Khosrojerdi, A., Rahmani-Kukia, N., Heidari, N., Abbasi, A., & Soudi, S. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1280601 · Cited by 27
Improving efficacy of TNBC immunotherapy: based on analysis and subtyping of immune microenvironment
Yang, Y., Li, H., Yang, W., & Shi, Y. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1441667 · Cited by 26
Plasticity and Functional Heterogeneity of Cancer-Associated Fibroblasts
Flynn, J. M., Thadani, N., Gallagher, E. E., Azzaro, I., Bodnar, C. M., McCarty, C. P., Romano, G., Webster, M. R., & Capparelli, C. (2025) · Cancer Research · doi:10.1158/0008-5472.can-24-3037 · Cited by 30
Understanding the Immune-Stroma Microenvironment in B Cell Malignancies for Effective Immunotherapy
Apollonio, B., Ioannou, N., Papazoglou, D., & Ramsay, A. G. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.626818 · Cited by 27
Feng, T., Fang, F., Zhang, C., Li, T., He, J., Shen, Y., Yu, H., & Liu, X. (2022) · Frontiers in Bioscience-Landmark · doi:10.31083/j.fbl2703104 · Cited by 26
“…evidence showed that the cancer cells are the most crucial factor for educating normal fibroblasts (NFs) to CAFs [12]; those research suggested that there was cellular cross-talk between CAFs and cancer cells [13,14]; however, the potential candidate activating fibroblasts is far from clear.”
BackgroundMakutani, Y., Kawakami, H., Tsujikawa, T., Yoshimura, K., Chiba, Y., Ito, A., Kawamura, J., Haratani, K., & Nakagawa, K. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.956270 · Cited by 30
“These findings suggest that further investigation of the TME, including both immune cells and mesenchymal or other stromal components, is required to better characterize the biology of colorectal cancer and to inform the development of new treatment strategies based on a better stratification of stage III colorectal c…”
BackgroundInfluentialStein, A. F. V., Rebollido-Rios, R., Lukas, A., Koch, M., von Lom, A., Reinartz, S., Bachurski, D., Rose, F., Bożek, K., Abdallah, A. T., et al. (2023) · Nature Communications · doi:10.1038/s41467-023-36824-2 · Cited by 27
Salminen, A. (2023) · Biogerontology · doi:10.1007/s10522-023-10072-9 · Cited by 27
“…different immune phenotypes, such as the inflammatory CAFs (iCAF), the immunosuppressive myofibroblast population (myCAF), the antigen-presenting CAFs (apCAF), and the complement-secreting CAFs (csCAF) (Costa et al. 2018; Mhaidly and Mechta-Grigoriou 2020; Bryce et al. 2022; Ngwenyama et al. 2022).”
BackgroundHong, M., Fan, S., Xu, Z., Fang, Z. Y., Ling, K., Lai, P. H., Han, C., Chen, Z., Hou, J., Liang, Y., et al. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05619-4 · Cited by 25
“This observation indicates that tumors may suppress effective immune cell infiltration through specific mechanisms, thereby diminishing the body’s immune response to the tumor and resulting in a poorer prognosis [35].”
BackgroundExtracellular matrix re-normalization to improve cold tumor penetration by oncolytic viruses
Soko, G. F., Kosgei, B. K., Meena, S. S., Ng, Y. J., Liang, H., Zhang, B., Liu, Q., Xu, T., Hou, X., & Han, R. P. S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1535647 · Cited by 25
“A variety of signals, such as TGF-b , OX40L, PD1, prostaglandin E2 (PGE2), and B7-H3, mediate the cross-talk between CAFs and tumor-in fi ltrating immune cells, which is crucial for the maintenance of the CAF phenotype and the transition among the different CAF subtypes (92, 100).”
Tumor-instructed glutamine synthesis in cancer-associated fibroblasts promotes pro-tumor macrophages
Li, X., Møller, S. H., Park, J., Chuang, Y., Hsueh, P., Chang, T.-H., Kao, K., Gallart‐Ayala, H., Wang, Y., Peng, J.-J., et al. (2025) · The Journal of Experimental Medicine · doi:10.1084/jem.20241426 · Cited by 27
Insights into the relevance of targeting fibroblasts to control cancer
Boeker, V., & Kalluri, R. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102395 · Cited by 25
“24 Furthermore, CAFs influence angiogenesis through secretion of pro-angiogenic factors like VEGF-A and VEGF/VEGFR, as modulated by proteins including hypoxia-induced angiogenesis regulator protein, or transform into a VEGF-A-secreting phenotype.”
Musa, M., & Ali, A. (2020) · Future Oncology · doi:10.2217/fon-2020-0384 · Cited by 26
A Scaffold-Free 3-D Co-Culture Mimics the Major Features of the Reverse Warburg Effect In Vitro
Keller, F., Bruch, R., Schneider, R., Meier-Hubberten, J. C., Hafner, M., & Rudolf, R. (2020) · Cells · doi:10.3390/cells9081900 · Cited by 24
“While cancer cells eventually enter a neoplastic state through reduced restrictions of proliferative potential [15], a metabolic shift of fibroblasts can bring these cells from a suppressive to a cancer-supportive state [16].”
Duan, R., Li, X., Zeng, D., Chen, X., Shen, B., Zhu, D., Zhu, L., Yu, Y., & Wang, D. (2021) · Frontiers in Immunology · doi:10.3389/fimmu.2020.609337 · Cited by 26
“It is well-known that Th1 cells activate antitumor immunity while fibroblasts suppress it (25, 26).”
BackgroundB cell/stromal cell crosstalk in health, disease, and treatment: Follicular lymphoma as a paradigm
Lamaison, C., & Tarte, K. (2021) · Immunological Reviews · doi:10.1111/imr.12983 · Cited by 24
Characterisation of the Stromal Microenvironment in Lobular Breast Cancer
Gómez-Cuadrado, L., Bullock, E., Mabruk, Z., Zhao, H., Souleimanova, M., Noer, P. R., Turnbull, A., Oxvig, C., Bertos, N., Byron, A., et al. (2022) · Cancers · doi:10.3390/cancers14040904 · Cited by 25
“their biological and clinical importance and also whether the heterogeneity and different sub-populations of CAFs that exist in other breast cancers are pertinent to ILC [50,51].”
BackgroundThe Role of PRMT5 in Immuno-Oncology
Abe, Y., Sano, T., & Tanaka, N. (2023) · Genes · doi:10.3390/genes14030678 · Cited by 30
“A type of CAF (CAF-S1), which express α-smooth muscle actin (α-SMA) and fibroblast activation protein (FAP), also recruits Tregs into the tumor [7].”
BackgroundYanagawa, J., Tran, L. M., Salehi‐Rad, R., Lim, R. J., Dumitras, C., Fung, E., Wallace, W. D., Prosper, A. E., Fishbein, G. A., Shea, C. V., et al. (2023) · Cancer Research · doi:10.1158/0008-5472.can-23-0128 · Cited by 30
“Recent studies identified FAPSMACD29 CAF, named as CAF subtype 1 (CAF-S1), which mediated immunosuppression in breast cancer (40).”
The role of immunosuppressive myofibroblasts in the aging process and age-related diseases
Salminen, A. (2023) · Journal of Molecular Medicine · doi:10.1007/s00109-023-02360-1 · Cited by 26
“Many single-cell transcriptional experiments have been conducted to characterize CAFs, FAFs, and WAFs [19–21].”
InfluentialApplication of Atlas of Cancer Signalling Network in preclinical studies
Gómez, L. C. M., Kondratova, M., Ravel, J., Barillot, E., Zinovyev, A. Y., & Kuperstein, I. (2018) · Briefings in Bioinformatics · doi:10.1093/bib/bby031 · Cited by 26
Comorbidity and social phobia: clinical and epidemiological issues.
Lépine, J., & Pélissolo, A. (1996) · PubMed · Cited by 25
Phenotypic and spatial heterogeneity of CD8+ tumour infiltrating lymphocytes
Sun, Y., Yinwang, E., Wang, S., Wang, Z., Wang, F., Xue, Y., Zhang, W., Zhao, S., Mou, H., Chen, S., et al. (2024) · Molecular Cancer · doi:10.1186/s12943-024-02104-w · Cited by 29
“…resolutions, where, using six fibroblast markers, they ascertained one particular myoCAF subset that tends to cluster near epithelial tumour cells in TNBCs and attracted, maintained, and differentiation into CD25 high FOXP3 high T REG s with augmented suppressive effects on CD8 + T cells [234].”
BackgroundZhang, X., Wang, Y., Cui, W., Li, D., Song, J., Liu, Y., Liu, Y., & Yang, S. (2025) · Drug Resistance Updates · doi:10.1016/j.drup.2025.101273 · Cited by 26
Fan, C., Zhu, W., Chen, Y., Zhu, W., & Ding, J. (2025) · MedComm · doi:10.1002/mco2.70415 · Cited by 30
Galván, J. A., Wiprächtiger, J., Slotta‐Huspenina, J., Feith, M., Ott, K., Kröll, D., Seiler, C. A., & Langer, R. (2019) · Archiv für Pathologische Anatomie und Physiologie und für Klinische Medicin · doi:10.1007/s00428-019-02714-6 · Cited by 21
Recent Advances in Nanotechnology for Dendritic Cell-Based Immunotherapy
Qian, C., Yang, L.-J., & Cui, H. (2020) · Frontiers in Pharmacology · doi:10.3389/fphar.2020.00960 · Cited by 24
Wu, J., Long, Y., Li, M., & He, Q. (2021) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2020.11.024 · Cited by 24
Organ Specificity and Heterogeneity of Cancer-Associated Fibroblasts in Colorectal Cancer
Miyashita, N., & Saito, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222010973 · Cited by 27
Gu, S., Xu, J., Teng, W., Huang, X., Mei, H., Chen, X., Nie, G., Cui, Z., Liu, X., Zhang, Y., et al. (2021) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2021.11.186 · Cited by 24
Mollah, F., & Varamini, P. (2021) · Biomedicines · doi:10.3390/biomedicines9121921 · Cited by 24
“CAV1, CD29/integrin β1 and fibroblast-specific protein 1 (FSP1)/S100-A4 have been used as markers of BCAFs [41].”
BackgroundMethodResultInfluentialQin, H., Lu, Y., Du, L., Shi, J., Yin, H., Jiang, B., Chen, W., Diao, W., Ding, M., Cao, W., et al. (2022) · Cancer Cell International · doi:10.1186/s12935-022-02467-4 · Cited by 24
Huynh, N. C., Huang, T., Nguyen, C. T.-K., & Lin, F.-K. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23126470 · Cited by 26
“These cells shared characteristics with previous myCAFs, iCAFs, and apCAFs identified by sc-RNAseq, bulk RNAseq, and functional experiments in pancreatic cancer and breast cancer [14,15,26].”
BackgroundSharpe, B. P., Hayden, A. L., Manousopoulou, A., Cowie, A., Walker, R., Harrington, J., Izadi, F., Breininger, S. P., Gibson, J., Pickering, O. J., et al. (2022) · Cell Reports Medicine · doi:10.1016/j.xcrm.2022.100541 · Cited by 29
“9 55 By reducing the transdiffer-entiation of fibroblasts in cancer and by modulating the phenotype of activated CAFs, we may be able to improve overall survival by several different mechanisms: improving response to chemo/immunotherapy, increasing tumor cell recognition by the immune system, and…”
Franzén, A. S., Raftery, M. J., & Pecher, G. (2022) · Cancers · doi:10.3390/cancers14133178 · Cited by 24
“These findings show an immunosuppressive role of the CAF-S1 subtype which could not be confirmed in the other fibroblast subtypes [29].”
BackgroundImmunomodulatory effects of regorafenib: Enhancing the efficacy of anti-PD-1/PD-L1 therapy
Liu, J., Tao, H., Yuan, T., Li, J., Li, J., Liang, H., Huang, Z., & Zhang, E. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.992611 · Cited by 27
“For example, CAFs recruit and activate Tregs by secreting regulators such as CXCL12 and CD73, thereby suppressing the function of effector T cells and promoting the formation of an immunosuppressive microenvironment (125).”
BackgroundDittmer, A., & Dittmer, J. (2022) · Cancers · doi:10.3390/cancers14204983 · Cited by 24
“In human BCs, four different subtypes of CAFs have been identified, which are not distinguished by their abilities to secret IL-6 but rather by the expression of other proteins, including the cytokines SDF1 and CCL11 [59].”
BackgroundEnhancing personalized immune checkpoint therapy by immune archetyping and pharmacological targeting
Cerella, C., Dicato, M. A., & Diederich, M. F. (2023) · Pharmacological Research · doi:10.1016/j.phrs.2023.106914 · Cited by 24
Olazaba, O. L., Farrow, J., & Monkkonen, T. (2024) · Frontiers in Genetics · doi:10.3389/fgene.2024.1304853 · Cited by 30
Henon, C., Vibert, J., Eychenne, T., Gruel, N., Daage, L. C., Ngo, C., Garrido, M., Dorvault, N., Costa, M. E. M. D., Marty, V., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101582 · Cited by 30
Reflections on depletion of tumor stroma in pancreatic cancer
Wang, W.-Q., Liu, L., Xu, J.-Z., & Yu, X. (2019) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2019.01.007 · Cited by 24
Lebdai, S., Gigoux, M., Alvim, R. G., Somma, A. J., Nagar, K. K., Azzouzi, A.-R., Cussenot, O., Merghoub, T., Wolchok, J. D., Scherz, A. J., et al. (2019) · OncoImmunology · doi:10.1080/2162402x.2019.1581528 · Cited by 23
“For example, other mechanisms of immunologic suppression were not addressed in this study, such as hypoxia, the presence of newly identified immunosuppressive cancer-associated fibroblasts, as well as other mechanisms.(10,38,39) Nevertheless, it has been shown that CSF1R inhibition attenuates the turnover rate of TAMs…”
ResultReactive stroma and trastuzumab resistance in HER2‐positive early breast cancer
Sonnenblick, A., Salmon‐Divon, M., Salgado, R., Dvash, E., Ponde, N. F., Zahavi, T., Salmon, A. Y., Loibl, S., Denkert, C., Joensuu, H., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.32859 · Cited by 23
“In addition, four CAFs with six concomitant analyses of six fibroblast markers(10) accumulate differently in breast cancer, making any such analysis more difficult.(10) Another limitation of our study is that reactive stroma was evaluated using full-face H&E-stained sections, in contrast to the practical more routine…”
BackgroundMethodResultInfluentialRavensbergen, C. J., Polack, M., Roelands, J. P., Crobach, S., Putter, H., Gelderblom, H. A. J., Tollenaar, R. A. �. �., & Mesker, W. E. (2021) · Cells · doi:10.3390/cells10112935 · Cited by 25
Hagens, M. J., van Leeuwen, P. J., Wondergem, M., Boellaard, T. N., Sanguedolce, F., Oprea‐Lager, D. E., Bex, A., Vis, A. N., van der Poel, H. G., & Mertens, L. S. (2024) · Journal of Nuclear Medicine · doi:10.2967/jnumed.123.267260 · Cited by 23
“Distinguishing themselves from normal fi broblasts, most cancer-associated fi broblasts exhibit remarkable overexpression of the fi broblast activation protein (FAP), making them an appealing target for noninvasive molecular imaging techniques ( 15,16 ).”
BackgroundMolecular adaptation to neoadjuvant immunotherapy in triple-negative breast cancer
Denkert, C., Schneeweiss, A., Rey, J., Karn, T., Hattesohl, A., Weber, K. E., Rachakonda, S., Braun, M., Huober, J., Jank, P., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101825 · Cited by 24
Current status and innovative developments of CAR-T-cell therapy for the treatment of breast cancer
Marei, H. E. S., Bedair, K., Hasan, A., Al-Mansoori, L., Caratelli, S., Sconocchia, G., Gaiba, A., & Cenciarelli, C. (2025) · Cancer Cell International · doi:10.1186/s12935-024-03615-8 · Cited by 26
“Tumor growth, invasion, neoangiogenesis, inflammation, immunological suppression, and extracellular matrix remodeling are all significantly influenced by CAFs, or stromal cells, in the breast TME [146].”
The role of CAFs in therapeutic resistance in triple negative breast cancer: an emerging challenge
Brogna, M. R., Varone, V., DelSesto, M., & Ferrara, G. (2025) · Frontiers in Molecular Biosciences · doi:10.3389/fmolb.2025.1568865 · Cited by 23
The plasticity of cancer-associated fibroblasts
Xia, Z., & Wever, O. D. (2025) · Trends in cancer · doi:10.1016/j.trecan.2025.04.012 · Cited by 27
Single-cell analysis on stromal fibroblasts in the microenvironment of solid tumours
Musa, M. (2020) · Advances in Medical Sciences · doi:10.1016/j.advms.2019.12.001 · Cited by 23
Roscigno, G., Cirella, A., Affinito, A., Quintavalle, C., Scognamiglio, I., Palma, F., Ingenito, F., Nuzzo, S., Micco, F. D., Cuccuru, A., et al. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21072313 · Cited by 23
“These cells release inflammatory cytokines, leading to the activation of pathways enhancing proliferation and stemness maintenance of cancer cells [22].”
BackgroundChemokine signaling in cancer-stroma communications
Singh, A. J., & Gray, J. W. (2021) · Journal of Cell Communication and Signaling · doi:10.1007/s12079-021-00621-7 · Cited by 23
Prognostic Interactions between FAP+ Fibroblasts and CD8a+ T Cells in Colon Cancer
Herrera, M., Mezheyeuski, A., Villabona, L. E. E., Corvigno, S., Strell, C., Klein, C., Hölzlwimmer, G., Glimelius, B. L. G., Masucci, G. V., Sjöblom, T., et al. (2020) · Cancers · doi:10.3390/cancers12113238 · Cited by 23
“Immune-regulatory mechanisms remain to be fully identified but have been suggested to include the secretion of immune-modulatory CXCL12; the expression of OX40L, PD-L2 and JAM2 and the induction of CTLA4 and PD1 in regulatory T cells [12,16,25].”
BackgroundInfluentialSpatial genomics maps the structure, character and evolution of cancer clonesPreprint
Lomakin, A., Svedlund, J., Strell, C., Gatarić, M., Shmatko, A., Park, J. S., Ju, Y. S., Dentro, S. C., Kleshchevnikov, V., Vaskivskyi, V., et al. (2021) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2021.04.16.439912 · Cited by 23
Zhou, D., & Zheng, L. (2024) · Chinese Medical Journal · doi:10.1097/cm9.0000000000003031 · Cited by 23
“Costa et al [35] used six biomarkers, namely FAP, integrin β 1, α -SMA, FSP-1, PDGFR β , and caveolin-1 (Cav-1), to define four subtypes of CAFs in breast cancer: CAF S1–S4.”
MethodCAFs vs. TECs: when blood feuds fuel cancer progression, dissemination and therapeutic resistance
Coursier, D., & Calvo, F. (2024) · Cellular Oncology · doi:10.1007/s13402-024-00931-z · Cited by 23
“Within this group, some studies classified ECM remodel - ing, wound healing-associated features (e.g. contractility) and TGFβ-signaling as distinct subgroups [ 32].”
BackgroundMechanoimmunology in the solid tumor microenvironment
Golo, M., Newman, P. L. H., Kempe, D., & Biro, M. (2024) · Biochemical Society Transactions · doi:10.1042/bst20231427 · Cited by 23
New insights into healthy ageing, inflammageing and frailty using metabolomics
Abdullah, G. A., Akpan, A., Phelan, M. M., & Wright, H. L. (2024) · Frontiers in Aging · doi:10.3389/fragi.2024.1426436 · Cited by 22
Advancements in melanoma immunotherapy: the emergence of Extracellular Vesicle Vaccines
He, G., Li, Y., Zeng, Y., Zhang, Y., Jiang, Q., Zhang, Q., Zhu, J., & Gong, J. (2024) · Cell Death Discovery · doi:10.1038/s41420-024-02150-9 · Cited by 26
“Fibroblast activation protein-α (FAP), is highly expressed in CAFs within various tumor tissues, and is considered a crucial molecule engaging in TME remodeling and tumor evolution [100].”
BackgroundLeonard, N. A., Corry, S. M., Reidy, E., Egan, H., O’Malley, G., Thompson, K., McDermott, E. A., O’Neill, A., Zakaria, N., Egan, L. J., et al. (2024) · iScience · doi:10.1016/j.isci.2024.110701 · Cited by 22
Sheng, N., Shindo, K., Ohuchida, K., Shinkawa, T., Zhang, B., Feng, H., Yamamoto, T., Moriyama, T., Ikenaga, N., Nakata, K., et al. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-1004 · Cited by 22
Liu, L., Wan, W., Chang, Y., Ao, L., Xu, Y., & Xu, X. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03527-z · Cited by 27
Remodeling the tumor dormancy ecosystem to prevent recurrence and metastasis
Liang, Y., Chen, W., Zhang, Y., & Li, L. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-025-02328-2 · Cited by 29
“120 – 122 Unlike normal breast fi broblasts, which fail to induce EMT in mammary epithelial carcinoma cells, CAFs promote EMT and enhance invasiveness through CXCL12 secretion and α - SMA activation.”
Lymph Node Stromal Cells: Mapmakers of T Cell Immunity
Harlé, G., Kowalski, C., Garnier, L., & Hugues, S. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21207785 · Cited by 26
Strell, C., Tullberg, A. S., Edelmann, R. J., Akslen, L. A., Malmström, P., Fernö, M., Holmberg, E. C., Östman, A., & Karlsson, P. (2021) · Breast Cancer Research and Treatment · doi:10.1007/s10549-021-06136-4 · Cited by 22
“1 3 In invasive breast cancer, a comprehensive IHC analysis approach recently identified four functional different fibroblast subsets [38], of which one subset was high in fibroblast activation protein (FAP) and PDGFRb expression and functionally linked to immunosuppression and pro-invasive effects [37, 38].”
BackgroundSingle‐cell advances in stromal‐leukocyte interactions in cancer
Wu, S. Z., & Swarbrick, A. (2021) · Immunological Reviews · doi:10.1111/imr.12976 · Cited by 21
An Optimized Method for Skin Cancer Diagnosis Using Modified Thermal Exchange Optimization Algorithm
Liu, W., Pan, S. X., Nanehkaran, Y. A., & Rajinikanth, V. (2021) · Computational and Mathematical Methods in Medicine · doi:10.1155/2021/5527698 · Cited by 22
“Based on the WHO reports, melanoma with 15000 cases is ranked as the fourth prevalent cancer and with 1900 cases is the ninth deadliest cancer [8].”
BackgroundPancreatic Adenocarcinoma Therapeutics Targeting RTK and TGF Beta Receptor
Yang, H.-H., Liu, J., Lee, J.-H., Harn, H., & Chiou, T. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22158125 · Cited by 22
Liu, J., Wang, X., Deng, Y., Yu, X., Wang, H., & Li, Z. (2021) · Frontiers in Oncology · doi:10.3389/fonc.2021.766248 · Cited by 23
“(116), multicolor flow cytometry and principal component analysis were”
BackgroundČelešnik, H., & Potočnik, U. (2022) · Cancers · doi:10.3390/cancers14030591 · Cited by 25
“CAF-S1 fibroblasts were found to promote an immunosuppressive environment by increasing the capacity of Tregs to inhibit T effector proliferation, by attracting (via CXCL12 secretion) and retaining CD4+CD25+ TILs, and by promoting their differentiation into CD25+FOXP3+ TILs [48].”
BackgroundInfluentialThe recent advances of cancer associated fibroblasts in cancer progression and therapy
Wu, C., Gu, J., Gu, H., Zhang, X.-X., Zhang, X., & Ji, R. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.1008843 · Cited by 24
“In breast cancer, CAF-S1 enhanced the ability of Tregs to suppress T effector proliferation, and then promoted immunosuppressive (65).”
BackgroundHeterotypic signaling of cancer-associated fibroblasts in shaping the cancer cell drug resistance
Butti, R., Khaladkar, A., Bhardwaj, P., & Prakasam, G. (2023) · Cancer Drug Resistance · doi:10.20517/cdr.2022.72 · Cited by 23
FAP-targeted PET imaging in gastrointestinal malignancies: a comprehensive review
Öztürk, A. A., & Flamen, P. (2023) · Cancer Imaging · doi:10.1186/s40644-023-00598-z · Cited by 23
“However, it still remains unclear whether this CAF-medi-ated immunosuppressive function is relevant in human tumours and if so, what are the mechanisms involved [57].”
BackgroundLi, T., Zhang, J., Yan, Y., Tan, M., & Chen, Y. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2024.1358070 · Cited by 22
“A series of histopathologic analyses demonstrated strong-to-moderate FAP expression is present in the stroma of breast carcinomas (78, 79).”
BackgroundNano-Drug Delivery Systems Targeting CAFs: A Promising Treatment for Pancreatic Cancer
Wang, M., Xue, W., Yuan, H., Wang, Z., & Yu, L. (2024) · International Journal of Nanomedicine · doi:10.2147/ijn.s451151 · Cited by 24
Tumor Microenvironment Modulation by Cancer-Derived Extracellular Vesicles
Ten, A., Kumeiko, V. V., Farniev, V. M., Gao, H., & Shevtsov, M. A. (2024) · Cells · doi:10.3390/cells13080682 · Cited by 25
“Depending on the expression of CAF markers (i.e., FAP, α SMA, and integrin β 1 [CD29]), various CAF subsets were previously identified for ovarian and breast cancers [137–139].”
BackgroundRicci, B., Tycksen, E., Celik, H., Belle, J. I., Fontana, F., Civitelli, R., & Faccio, R. (2020) · eLife · doi:10.7554/elife.54659 · Cited by 22
Microenvironmental regulation of tumour immunity and response to immunotherapy
Kockx, M. M., McCleland, M. L., & Koeppen, H. (2021) · The Journal of Pathology · doi:10.1002/path.5681 · Cited by 23
Impact of B cell/lymphoid stromal cell crosstalk in B-cell physiology and malignancy
Lamaison, C., & Tarte, K. (2019) · Immunology Letters · doi:10.1016/j.imlet.2019.02.005 · Cited by 21
desJardins-Park, H. E., Chinta, M. S., Foster, D. S., Borrelli, M. R., Shen, A. H., Wan, D. C., & Longaker, M. T. (2020) · Plastic & Reconstructive Surgery Global Open · doi:10.1097/gox.0000000000002927 · Cited by 22
Wang, S., & Hamian, M. (2021) · Computational Intelligence and Neuroscience · doi:10.1155/2021/9528664 · Cited by 21
“Based on the statistical information for 2019, skin cancer with 15000 cases is ranked as the fourth most common cancer, and with 1900 deaths cases are ranked as one of the 10th common cancers in the world [4].”
BackgroundVallejo-Armenta, P., Ferro‐Flores, G., Santos‐Cuevas, C., García-Pérez, F. O., Casanova-Triviño, P., Sandoval-Bonilla, B. A., Ocampo‐García, B., Azorin‐Vega, E. P., & Luna‐Gutiérrez, M. (2022) · Pharmaceuticals · doi:10.3390/ph15060729 · Cited by 21
“CAFs are abundant in mesothelial metastases, and, through the mesothelial-mesenchymal transformation mechanism, it is likely that in carcinomatosis there is a greater transdifferentiation of mesenchymal cells towards CAFs FAP+ [14].”
BackgroundInfluentialZhou, Y., Tian, Q., Gao, H., Zhu, L., Zhang, Y., Zhang, C., Yang, J., & Wang, B. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.859581 · Cited by 21
“Among TILs, not only CTLs but also CD4+ helper T (TH) cells direct ly or indirect ly exert protumorigenic or/and antitumorigenic immune effects by affecting other immune cells, especially CTLs, through the inflammatory molecules secreted by different subtypes of TH cells and the accommodation of signal transduction (1…”
BackgroundBarrera, L. N., Ridley, P., Bermejo‐Rodríguez, C., Costello, E., & Pérez-Mancera, P. A. (2022) · Journal of Physiology and Biochemistry · doi:10.1007/s13105-022-00899-0 · Cited by 22
“The rapid development of next-generation sequencing technologies is shedding new light on the existence of diverse CAF subtypes, with different activities, within the tumour microenvironment [21, 29, 35, 57, 63, 65, 94, 119].”
BackgroundBonneaud, T. L., Lefebvre, C. C., Nocquet, L., Basseville, A., Roul, J., Weber, H., Campone, M., Juin, P. P., & Souazé, F. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05214-9 · Cited by 23
“Subsets with myofibroblastic characteristics are enriched in tumor tissue and contribute to pathogenesis [3, 4].”
BackgroundA skin cancer diagnosis system for dermoscopy images according to deep training and metaheuristics
Huang, Q., Ding, H. W., & Sheykhahmad, F. R. (2023) · Biomedical Signal Processing and Control · doi:10.1016/j.bspc.2023.104705 · Cited by 21
FDG and Non-FDG Radiopharmaceuticals for PET Imaging in Invasive Lobular Breast Carcinoma
Gilardi, L., Farulla, L. S. A., Curigliano, G., Corso, G., Leonardi, M. C., & Ceci, F. (2023) · Biomedicines · doi:10.3390/biomedicines11051350 · Cited by 21
“…cell type of BC TME and constitute a heterogeneous population divided into four groups (CAF-S1 to CAF-S4) according to differential activation marker expression of α -smooth muscle actin (ASMA), fibroblast activation protein (FAP), platelet-derived growth factor (PDGF) receptor β , and CD29 [76].”
BackgroundLi, M., Wu, B., Li, L., Lv, C., & Tian, Y. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.188945 · Cited by 23
Sekiguchi, S., Yorozu, A., Okazaki, F., Niinuma, T., Takasawa, A., Yamamoto, E., Kitajima, H., Kubo, T., Hatanaka, Y., Nishiyama, K., et al. (2023) · Cancers · doi:10.3390/cancers15174303 · Cited by 22
Carretta, M., Thorseth, M., Schina, A., Agardy, D. A., Johansen, A. Z., Baker, K. J., Khan, S., Rømer, A. M. A., Fjæstad, K. Y., Linder, H., et al. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1320614 · Cited by 21
Cancer-Associated Fibroblast Heterogeneity in Malignancy with Focus on Oral Squamous Cell Carcinoma
Arebro, J., Lee, C.-M., Bennewith, K. L., & Garnis, C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25021300 · Cited by 25
“In fact, they have also shown that CAF-S1 fibroblasts themselves have eight distinct subtypes within that subset, some of which fit the myCAF/iCAF nomenclature [7].”
BackgroundInfluentialDésigaux, T., Comperat, L., Dusserre, N., Stachowicz, M., Lea, M., Dupuy, J., Vial, A., Molinari, M., Fricain, J., Paris, F., et al. (2024) · Bioactive Materials · doi:10.1016/j.bioactmat.2024.08.037 · Cited by 24
“Our study is based on a subtype S3 CAF cell line, present in juxta-tumoral tissues [45], relevant to our model geometry and poorly described until now.”
Ren, F., Meng, L., Zheng, S., Cui, J., Song, S., Li, X., Wang, D., Li, X., Liu, Q., Bu, W., et al. (2025) · Journal of Experimental & Clinical Cancer Research · doi:10.1186/s13046-025-03290-1 · Cited by 21
Macrophage heterogeneity and its interactions with stromal cells in tumour microenvironment
Cao, L., Meng, X., Zhang, Z., Liu, Z., & He, Y. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01201-z · Cited by 28
“Fibroblasts constitute the most abundant stromal components of the TME, favouring immunosuppressive TME formation [82, 83].”
BackgroundMiao, N., Kang, Z., Wang, Z., Yu, W., Liu, T., Kong, L.-Z., Zheng, Y., Ding, C., Zhang, Z., Zhong, C., et al. (2025) · Cell Death Discovery · doi:10.1038/s41420-025-02516-7 · Cited by 20
“Nonetheless, the ef fi cacy of anti-tumor immunity is often compromised by the immunosuppressive characteristics of the TME in numerous breast cancer patients [7, 8].”
Gao, H., Wong, S. T. C., Subel, E. J., Huang, Y.-H., Lee, Y., Hayashi, K., Alonzo, M. E., Karabicici, M., Hoi, X. P., Kasabyan, A., et al. (2025) · Science Advances · doi:10.1126/sciadv.adt8697 · Cited by 20
“Alternatively, interleukin-6 high (IL-6 high ) CAFs, which lack ACTA2 ( α SMA − ), were classified as inflammatory CAFs (iCAFs; α SMA − IL-6 high ) ( 21 , 22 ). α SMA + /high CAFs have also been reported to coexpress IL-6 ( α SMA high IL-6 high ), contributing to chemoresistance ( 23 ).”
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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