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]
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Items 401–500 of 1,002
Cancer associated fibroblasts as novel promising therapeutic targets in breast cancer
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“CAF-S1 is associated with accumulation of FOXP3+ T Lymphocytes and enhances regulatory T cell differentiation through B7H3, CD73, and DPP4 (89).”
BackgroundPerivascular niches: critical hubs in cancer evolution
Nowosad, A., Marine, J., & Karras, P. (2023) · Trends in cancer · doi:10.1016/j.trecan.2023.06.010 · Cited by 60
Cancer-associated fibroblasts drive CXCL13 production in activated T cells via TGF-beta
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“CAF can influence adaptive immunity in many ways, some negative: retaining T cells in the stroma and preventing migration into the tumour islets (31), limiting proliferation, promoting Treg recruitment (32), and even directly killing activated T cells (33).”
BackgroundChuangchot, N., Jamjuntra, P., Yangngam, S., Luangwattananun, P., Thongchot, S., Junking, M., Thuwajit, P., Yenchitsomanus, P., & Thuwajit, C. (2023) · Breast Cancer Research · doi:10.1186/s13058-023-01684-7 · Cited by 58
Colorectal cancer-associated fibroblasts inhibit effector T cells via NECTIN2 signaling
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Regulatory T cells in breast cancer as a potent anti-cancer therapeutic target
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Extracellular matrix in cancer progression and therapy
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“Some CAFs additionally support tumor growth through mechanisms independent of ECM remodeling, such as promoting cancer stemness or preventing cancer cell recognition by T-cells [62, 63].”
BackgroundTargeting HIC1/TGF-β axis-shaped prostate cancer microenvironment restrains its progression
Wu, T., Wang, W., Shi, G., Hao, M., Wang, Y., Yao, M., Huang, Y., Du, L., Zhang, X., Ye, D., et al. (2022) · Cell Death and Disease · doi:10.1038/s41419-022-05086-z · Cited by 59
“By secreting CXCL12, CAFs attract conventional CD4 T cell migration through its receptor-CXCR4 and promotes their differentiation into Foxp3 regulatory T cells to create an immunosuppressive environment in human breast cancer [43].”
BackgroundCAF-immune cell crosstalk and its impact in immunotherapy
Maia, A. R. R., Schöllhorn, A., Schuhmacher, J., & Gouttefangeas, C. (2022) · Seminars in Immunopathology · doi:10.1007/s00281-022-00977-x · Cited by 61
“Additionally, gene expression analysis of CAFs from cancer patients shows a positive and negative correlation between myCAF-signatures and the infiltration of CTLA-4+CD4+ T cells and CD8+ T cells, respectively [42, 45].”
BackgroundZheng, S., Liang, J., Tang, Y., Xie, J., Zou, Y., Yang, A., Shao, N., Kuang, X., Ji, F., Liu, X., et al. (2023) · Clinical and Translational Medicine · doi:10.1002/ctm2.1189 · Cited by 57
“7 Moreover, CAFs may exhibit anti-tumorigenic effects under certain circumstances.”
Tong, W., Wang, T., Bai, Y., Yang, X., Han, P., Zhu, L., Zhang, Y., & Shen, Z. (2024) · Journal of Translational Medicine · doi:10.1186/s12967-024-05613-w · Cited by 59
“These CAFs play a pivotal role in driving tumor cell proliferation, invasion, and metastasis across various cancer types, including HCC [37, 38].”
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The fibroinflammatory response in cancer
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Human cutaneous neurofibroma matrisome revealed by single-cell RNA sequencing
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Targeting of the Cancer-Associated Fibroblast—T-Cell Axis in Solid Malignancies
Harryvan, T. J., Verdegaal, E. M. E., Hardwick, J. C. H., Hawinkels, L. J. A. C., & van der Burg, S. H. (2019) · Journal of Clinical Medicine · doi:10.3390/jcm8111989 · Cited by 55
“This particular fibroblast subset is detected in pancreatic, colorectal, ovarian, breast and lung cancer and is implicated in regulating the immune response, suggesting a shared biological mechanism amongst different solid malignancies [36,39,40,42,43].”
BackgroundResultInfluentialRoles of Reactive Oxygen Species in Biological Behaviors of Prostate Cancer
Han, C., Wang, Z., Xu, Y., Chen, S., Han, Y., Li, L., Wang, M., & Xun-bo, J. (2020) · BioMed Research International · doi:10.1155/2020/1269624 · Cited by 57
Subclonal heterogeneity and evolution in breast cancer
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Fight the Cancer, Hit the CAF!
Papait, A., Romoli, J., Stefani, F. R., Chiodelli, P., Montresor, M. C., Agoni, L., Silini, A. R., & Parolini, O. (2022) · Cancers · doi:10.3390/cancers14153570 · Cited by 55
Polyphenol-Based Nanoparticles: A Promising Frontier for Enhanced Colorectal Cancer Treatment
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“Additionally, polyphenols can indirectly inhibit tumor growth by influencing the behavior of cells in the tumor microenvironment [14].”
BackgroundSchütz, S., Solé‐Boldo, L., Lucena-Porcel, C., Hoffmann, J. H. O., Brobeil, A., Lonsdorf, A. S., Rodríguez‐Paredes, M., & Lyko, F. (2023) · Nature Communications · doi:10.1038/s41467-023-41141-9 · Cited by 59
“Furthermore, we showed that both CAF subtypes coexist in the TME, consistent with published fi ndings from different cancer entities 23,26,52,53 .”
ResultFibroblasts in Diabetic Foot Ulcers
Voza, F. A., Huerta, C. T., Le, N., Shao, H., Ribieras, A. J., Ortiz, Y. Y., Atkinson, C., Machuca, T., Liu, Z., & Velazquez, O. C. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25042172 · Cited by 62
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“Globally, all CAF could be divided in two major groups, the myCAF and iCAF, while they all belonged mainly to s1 type and none were of s4 type (as defined by Costa et al. [18]) ( Figure 1D ).”
BackgroundInfluentialCancer-Associated Fibroblasts in the Breast Tumor Microenvironment
Giorello, M. B., Borzone, F. R., Labovsky, V., Piccioni, F., & Chasseing, N. A. (2021) · Journal of Mammary Gland Biology and Neoplasia · doi:10.1007/s10911-020-09475-y · Cited by 58
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“Moreover, as a pivotal biomarker expressed in immune system, OX40 also serves as an important marker in associate with MEK, Dectin-1, RORγt+ CD8+ T Cells and other immune modulator in the anti-cancer immunology setting (76-82).”
BackgroundPancreatic Cancer and Its Microenvironment—Recent Advances and Current Controversies
Stopa, K. B., Kusiak, A. A., Szopa, M. D., Ferdek, P. E., & Jakubowska, M. A. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21093218 · Cited by 55
“Interestingly, CAFs may assume different phenotypes in distinct cancers/cancer compartments [104,109].”
BackgroundLi, M., Li, G., Kiyokawa, J., Tirmizi, Z. A., Richardson, L. G., Ning, J., Das, S., Martuza, R. L., Stemmer-Rachamimov, A. O., Rabkin, S. D., et al. (2020) · Acta Neuropathologica Communications · doi:10.1186/s40478-020-01096-0 · Cited by 59
Uncovering hypergraphs of cell-cell interaction from single cell RNA-sequencing dataPreprint
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Rubinstein-Achiasaf, L., Morein, D., Ben-Yaakov, H., Liubomirski, Y., Meshel, T., Elbaz, E., Dorot, O., Pichinuk, E., Gershovits, M., Weil, M., et al. (2021) · Cancers · doi:10.3390/cancers13061472 · Cited by 53
Itoh, G., Takagane, K., Fukushi, Y., Kuriyama, S., Umakoshi, M., Goto, A., Yanagihara, K., Yashiro, M., & Tanaka, M. (2021) · Molecular Oncology · doi:10.1002/1878-0261.13077 · Cited by 53
Meflin-positive cancer-associated fibroblasts enhance tumor response to immune checkpoint blockade
Miyai, Y., Sugiyama, D., Hase, T., Asai, N., Taki, T., Nishida, K., Fukui, T., Chen-Yoshikawa, T. F., Kobayashi, H., Mii, S., et al. (2022) · Life Science Alliance · doi:10.26508/lsa.202101230 · Cited by 55
“Single-cell analysis of tumor stroma provided evidence of similar CAF populations in other cancer types, such as breast and lung cancer (Costa et al, 2018; Lambrechts et al, 2018; Kieffer et al, 2020).”
BackgroundGao, D., Fang, L., Liu, C., Yang, M., Yu, X., Wang, L., Zhang, W., Sun, C., & Zhuang, J. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115622 · Cited by 52
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“PLA2G2A has been associated with poor survival in various cancers and has been implicated in the recruitment of immune cells 44,55 – 60 .”
BackgroundCancer-Associated Fibroblasts: Implications for Cancer Therapy
Maia, A. R. R., & Wiemann, S. (2021) · Cancers · doi:10.3390/cancers13143526 · Cited by 58
“showed that fibroblasts in breast cancer could be divided into four populations (CAFS1 to S4), according to the expression of commonly used markers such as FAPα, αSMA, FSP1, PDGFRβ and Caveolin, demonstrating an immunosuppressive role of CAF-S1 in the TME [37].”
BackgroundCancer-Associated Fibroblast Functions as a Road-Block in Cancer Therapy
De, P. K., Aske, J. C., & Dey, N. (2021) · Cancers · doi:10.3390/cancers13205246 · Cited by 54
“FAP-high CAFs are correlated with Treg cell-mediated immunosuppression and thus a poor outcome [44].”
BackgroundSakai, T., Aokage, K., Neri, S., Nakamura, H., Nomura, S., Tane, K., Miyoshi, T., Sugano, M., Kojima, M., Fujii, S., et al. (2018) · Lung Cancer · doi:10.1016/j.lungcan.2018.10.021 · Cited by 54
Cancer-associated fibroblasts in cholangiocarcinoma
Vaquero, J., Aoudjehane, L., & Fouassier, L. (2020) · Current Opinion in Gastroenterology · doi:10.1097/mog.0000000000000609 · Cited by 52
Piper, M., Mueller, A. C., & Karam, S. D. (2020) · Molecular Carcinogenesis · doi:10.1002/mc.23205 · Cited by 52
“Collectively, these effects result in a tumor microenvironment characterized by a highly immunosuppressive cytokine profile and reduced effector T cell function.(99,102) CAF, cancer associated fibroblast 758 | PIPER ET AL.”
BackgroundCancer-Associated Fibroblasts: Epigenetic Regulation and Therapeutic Intervention in Breast Cancer
Lee, Y. T., Tan, Y. J., Falasca, M., & Oon, C. E. (2020) · Cancers · doi:10.3390/cancers12102949 · Cited by 50
“Nevertheless, the absence of CAV1 expression in all BCAF subsets was found to be positively correlated with the constitutive activation of CAFs phenotype and poor prognosis in BC patients [10,38,50].”
BackgroundInfluentialTargeting cancer-associated fibroblasts: Challenges, opportunities and future directions
Jenkins, B. H., Buckingham, J. F., Hanley, C. J., & Thomas, G. J. (2022) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2022.108231 · Cited by 56
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Khouzam, R. A., Janji, B., Thiery, J., Zaarour, R. F., Chamseddine, A. N., Mayr, H., Savagner, P., Kiéda, C., Gad, S., Buart, S., et al. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.11.008 · Cited by 54
Xiao, Y., Hassani, M., Moghaddam, M. B., Fazilat, A., Ojarudi, M., & Valilo, M. (2025) · Medical Oncology · doi:10.1007/s12032-025-02675-8 · Cited by 58
“One of the most abundant stromal components in solid tumors are CAFs, which are identified by several markers including α-smooth muscle actin (α-SMA), fibroblast activating protein (FAP), and integrin β1 (CD29), among others [139, 140].”
Metabolic reprogramming of mitochondrial respiration in metastatic cancer
Herst, P. M., Grasso, C., & Berridge, M. V. (2018) · Cancer and Metastasis Reviews · doi:10.1007/s10555-018-9769-2 · Cited by 51
Cosentino, G., Plantamura, I., Tagliabue, E., Iorio, M. V., & Cataldo, A. (2021) · Cancers · doi:10.3390/cancers13153691 · Cited by 52
“For example, the presence of spatially and functionally distinct subsets of CAFs has been described in the breast TME, which also influence the composition of the immune compartment, thus impacting patient prognosis [33,34].”
BackgroundTumor microenvironment pathways: Cross regulation in breast cancer metastasis
Malla, R. R., & Kiran, P. J. (2020) · Genes & Diseases · doi:10.1016/j.gendis.2020.11.015 · Cited by 52
“CAFs increase the ability of regulatory T cells to inhibit the proliferation of T effector cells.(38) However, the proliferation of Tregs is distinctly inhibited by CDK4/6 inhibitors.”
BackgroundLoh, J. J., & Ma, S. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.727640 · Cited by 50
“A more holistic approach investigating the CAF molecular profile, for instance, epitranscriptomic and epigenetics (Delaunay and Frye, 2019; Song et al., 2020), may unravel novel insights into how CAF shuttles between cell types.”
BackgroundStrategies for Efficient Targeting of Tumor Collagen for Cancer Therapy
Baldari, S., Modugno, F. D., Nisticò, P., & Toietta, G. (2022) · Cancers · doi:10.3390/cancers14194706 · Cited by 53
“Different subsets of CAFs have been identified on the basis of their gene expression, phenotypic marker profiles and functions [17,18].”
BackgroundCao, J., Lv, G., & Wei, F. (2024) · Clinical and Translational Medicine · doi:10.1002/ctm2.1645 · Cited by 50
“52 In a notable study by Hu et al., a novel approach was introduced wherein FAP gene-engineered tumour cell-derived exosome-like nanovesicles (eNVs-FAP) were developed as a convenient and scalable tumour vaccine.”
BackgroundThe progress and prospects of targeting the adenosine pathway in cancer immunotherapy
Yang, Y., Zhu, L., Xu, Y., Liang, L., Liu, L.-Z., Chen, X., Li, H., & Liu, H. (2025) · Biomarker Research · doi:10.1186/s40364-025-00784-0 · Cited by 55
“A2BR signaling on CAFs also enhances CXCL12 secretion, which recruits Treg cells to the tumor and promotes T lymphocyte differentiation into CD25 high Foxp3 high subsets [144, 145], potentially fostering pro-tumor effects both autocrine and paracrine.”
Tumor Cells and Cancer-Associated Fibroblasts: An Updated Metabolic Perspective
Gentric, G., & Mechta‐Grigoriou, F. (2021) · Cancers · doi:10.3390/cancers13030399 · Cited by 52
Targeting stromal cell Syndecan‐2 reduces breast tumour growth, metastasis and limits immune evasion
Loftus, P., Watson, L., Deedigan, L., Camarillo‐Retamosa, E., Dwyer, R. M., O’Flynn, L., Alagesan, S., Griffin, M. D., O’Brien, T., Kerin, M. J., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.33383 · Cited by 49
Bhome, R., Emaduddin, M., James, V. H., House, L. M., Thirdborough, S. M., Mellone, M., Tulkens, J., Primrose, J. N., Thomas, G. J., Wever, O. D., et al. (2022) · Journal of Extracellular Vesicles · doi:10.1002/jev2.12226 · Cited by 52
“At a time when different CAF phenotypes are being discovered and characterised by single cell techniques, these data demonstrate a mechanism for what is being observed (Costa et al., 2018; Li et al., 2017).”
InfluentialPakravan, K., Mohammadi, M. M., Ghazimoradi, M. H., Cho, W. C. S., Sadeghizadeh, M., & Babashah, S. (2022) · Journal of Translational Medicine · doi:10.1186/s12967-022-03780-2 · Cited by 49
“Cancer-associated fibroblasts (CAFs), which are a prominent part of the tumor stroma, not only provide physical support for tumor cells to promote tumor growth and progression, but they also contribute to an immunosuppressive TME by affecting many immune cells [2, 3].”
BackgroundOra, M., Soni, N., Nazar, A. H., Dixit, M., Singh, R., Puri, S., Graham, M. M., & Gambhir, S. (2023) · Journal of Nuclear Medicine · doi:10.2967/jnumed.123.265594 · Cited by 49
“CAFs differ in biomarkers and FAP expression (2,29).”
BackgroundCarlo, S. E. D., Raffenne, J., Varet, H., Ode, A., Granados, D. C., Stein, M., Legendre, R., Tuckermann, J. P., Bousquet, C., & Peduto, L. (2023) · Nature Immunology · doi:10.1038/s41590-023-01642-7 · Cited by 51
“Tumor stromal cells express mesenchymal markers such as podoplanin (PDPN) and platelet-derived growth factor receptor alpha (PDGFR-α), and are highly heterogeneous, as has been shown by single cells RNA sequencing (RNA-seq) studies in several tumor types 9–11 .”
BackgroundThe inhibitory effect of adenosine on tumor adaptive immunity and intervention strategies
Wang, L., Zhang, J., Zhang, W., Zheng, M., Guo, H., Pan, X., Li, W., Yang, B., & Ding, L. (2023) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2023.12.004 · Cited by 56
“In solid tumors such as breast cancer, pancreatic cancer, ovarian cancer, and colorectal cancer, CAFs overexpress CD39 and CD73, leading to increased production of Ado 132 e 134 .”
BackgroundIdentification of a Potent Oridonin Analogue for Treatment of Triple-Negative Breast Cancer
Yao, H., Xie, S., Ma, X., Liu, J., Wu, H., Lin, A., Yao, H., Li, D., Xu, S., Yang, D., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00408 · Cited by 49
Zarychta, E., & Ruszkowska-Ciastek, B. (2022) · Biomedicines · doi:10.3390/biomedicines10020300 · Cited by 50
“They support the invasive growth of tumors, as opposed to normal fibroblasts, which block tumor formation [69,70].”
BackgroundFang, Z., Xu, J., Zhang, B., Wang, W., Liu, J., Liang, C., Hua, J., Meng, Q., Yu, X., & Shi, S. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00988-x · Cited by 47
Zhang, Y., Gu, Z., Wan, J., Lou, X., Liu, S., Wang, Y., Bian, Y., Wang, F., Li, Z., & Qin, Z. (2022) · International Journal of Biological Sciences · doi:10.7150/ijbs.74924 · Cited by 48
“Because of the non-specific markers, CAFs comprise many sub-types with different functions [3, 5].”
BackgroundZhang, S.-W., Wang, H., Xiao, Y. Q., Liu, L.-T., Shen, M., Wang, Z., Zhao, S., Ding, X.-H., Wang, Y., Zhuang, Q.-Y., et al. (2026) · Cell · doi:10.1016/j.cell.2026.01.001 · Cited by 52
Li, B., Pei, G., Yao, J., Ding, Q., Jia, P., & Zhao, Z. (2021) · Oncogene · doi:10.1038/s41388-021-01870-x · Cited by 48
“as opposed to other stroma components in Breast invasive carcinoma (BRCA) was relatively higher than other cancer types, which was consistent with the results from a previous study [22].”
ResultBreast Cancer CAFs: Spectrum of Phenotypes and Promising Targeting Avenues
Elwakeel, E., & Weigert, A. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms222111636 · Cited by 49
“The CAF-S1 subset was associated with an immune-suppressive environment via secretion of CXCLl12 and enhancing T cell differentiation to regulatory T cells (Tregs), while CAF-S4 subset was lacking such a phenotype [53].”
BackgroundTimperi, E., Croizer, H., Khantakova, D., Rana, M., Molgora, M., Guerriero, J. L., Mechta-Grigoriou, F., & Romano, E. (2024) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-24-1690 · Cited by 49
Gorchs, L., & Kaipe, H. (2021) · Cancers · doi:10.3390/cancers13122995 · Cited by 56
“Similarly, CAFs derived from other tumor types also promote the expression and recruitment of FOXP3+CD4+ T cells into the tumor milieu [41,106,107].”
BackgroundScripture-Adams, D. D., Chesmore, K. N., Barthélémy, F., Wang, R. T., Nieves‐Rodriguez, S., Wang, D. W., Mokhonova, E. I., Douine, E. D., Wan, J., Little, I., et al. (2022) · Communications Biology · doi:10.1038/s42003-022-03938-0 · Cited by 46
Targeting cancer-specific metabolic pathways for developing novel cancer therapeutics
Pal, S., Sharma, A. K., Mathew, S. P., & Jaganathan, B. G. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.955476 · Cited by 50
Salminen, A., Kaarniranta, K., & Kauppinen, A. (2024) · Ageing Research Reviews · doi:10.1016/j.arr.2024.102296 · Cited by 50
“…is not only liver and certain immune cells but also the fibroblasts present in several tissues can secrete complement components including those involved in the classical, alternative, or lectin pathways (Kulics et al., 1994; Ezure et al., 2019; Le Fournis et al., 2020; Friscic et al., 2021) (Fig.”
InfluentialPIK3Cδ expression by fibroblasts promotes triple-negative breast cancer progression
Gagliano, T., Shah, K., Gargani, S., Lao, L., Alsaleem, M. A., Chen, J., Ntafis, V., Huang, P., Ditsiou, A., Vella, V., et al. (2020) · Journal of Clinical Investigation · doi:10.1172/jci128313 · Cited by 49
“According to recent evidence (8), CAFs in TNBC should be characterized by the”
BackgroundRecent advances in understanding cancer-associated fibroblasts in pancreatic cancer
Huang, H., & Brekken, R. A. (2020) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00079.2020 · Cited by 49
An emerging role for cellular crosstalk in the cancer stem cell niche
Oshimori, N., Guo, Y., & Taniguchi, S. (2021) · The Journal of Pathology · doi:10.1002/path.5655 · Cited by 50
“Costa et al [22] identified four CAF subsets with differential properties and activation status.”
BackgroundBai, X., Ni, J., Beretov, J., Graham, P., & Li, Y. (2021) · Journal of the National Cancer Center · doi:10.1016/j.jncc.2021.06.001 · Cited by 50
Immune evasion in esophageal squamous cell cancer: From the perspective of tumor microenvironment
Li, R., Huang, B. Q., Tian, H., & Sun, Z. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2022.1096717 · Cited by 47
“Frontiers in Oncology 04 monocytes into myeloid-derived suppressor cells (MDSCs) by secreting IL-6 and signal transducer and activator of transcription 3 (STAT3) (44); stimulate CD4 T cells to differentiate into Tregs and Th2-type helper T cells (45), etc.”
BackgroundFibroblast Activation Protein Expression in Sarcomas
Crane, J. N., Graham, D. S., Mona, C. E., Nelson, S. D., Samiei, A., Dawson, D. W., Dry, S., Masri, M. G., Crompton, J. G., Benz, M., et al. (2023) · Sarcoma · doi:10.1155/2023/2480493 · Cited by 46
Zheng, J., & Hao, H. (2024) · Frontiers in Oncology · doi:10.3389/fonc.2023.1333839 · Cited by 49
“…and differentiation of CD4+CD25+ Treg in the TME through the CXCL12/SDF1-a pathway, thereby suppressing the function of effector T cells (33). a -SMA+ CAFs have been identi fi ed as an important cellular source of TGF-b , which hampers the cytotoxic activity of CD8+ T cells by…”
BackgroundInfluentialLi, Y., Wang, L., Ma, W., Wu, J., Wu, Q., & Sun, C. (2025) · Journal of Translational Medicine · doi:10.1186/s12967-025-06744-4 · Cited by 49
Therapeutic Potential of Tumor Metabolic Reprogramming in Triple-Negative Breast Cancer
Munkácsy, G., Santarpia, L., & Győrffy, B. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24086945 · Cited by 46
Xu, Y., Li, W., Lin, S., Liu, B., Wu, P., & Li, L. (2023) · Cell Communication and Signaling · doi:10.1186/s12964-023-01204-2 · Cited by 50
“Finally, it is viable to target CAFs-derived extracellular matrix proteins and related signaling to deplete the stroma and boost immunological T cell infiltration pathways [17, 49, 118, 158, 173, 178].”
BackgroundUnveiling the Immune Microenvironment’s Role in Breast Cancer: A Glimpse into Promising Frontiers
Kotsifaki, A., Alevizopoulos, N., Dimopoulou, V., & Armakolas, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms242015332 · Cited by 46
“These studies have explored diverse aspects ranging from novel therapeutic approaches and CIs to the role of specific immune cell populations within the TME [189–193].”
BackgroundImodoye, S. O., Adedokun, K. A., & Bello, I. O. (2024) · Histochemistry and Cell Biology · doi:10.1007/s00418-023-02258-6 · Cited by 47
“Four distinct classes of CAFs are differentially associated with various molecular subtypes of breast cancer, with CAF-S1 and CAF-S4 preferentially found in triple-negative breast cancer (Costa et al. 2018), the most aggressive breast tumor.”
Assessing personalized responses to anti-PD-1 treatment using patient-derived lung tumor-on-chip
Veith, I., Nurmik, M., Mencattini, A., Damei, I., Lansche, C., Brosseau, S., Gropplero, G., Corgnac, S., Filippi, J., Poté, N., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101549 · Cited by 49
“29–32 We added these allogeneic CAF-S1 (isolated from patient #2) into the autologous cancer-immune co-cultures (IGR-Heu and H5B).”
Sapudom, J., Müller, C. D., Nguyen, K.-T., Martin, S., Anderegg, U., & Pompe, W. (2020) · Gels · doi:10.3390/gels6040033 · Cited by 49
Mesenchymal stem cells induce PD‐L1 expression through the secretion of CCL5 in breast cancer cells
Es, H. A., Bigdeli, B., Zhand, S., Aref, A. R., Thiery, J. P., & Warkiani, M. E. (2020) · Journal of Cellular Physiology · doi:10.1002/jcp.30135 · Cited by 48
“…the critical role of CAFs in the induction of an immune‐suppressive TME through the regulation of the immune checkpoints particularly PD‐L1 in both themselves and cancer cells in‐vitro and in‐vivo (Aboulkheyr Es et al., 2020; Biswas et al., 2019; Costa et al., 2018; Lakins et al., 2018).”
BackgroundResultInfluentialO’Connor, R. A., Chauhan, V., Mathieson, L., Titmarsh, H. F., Koppensteiner, L., Young, I., Tagliavini, G., Dorward, D. A., Prost, S., Dhaliwal, K., et al. (2021) · OncoImmunology · doi:10.1080/2162402x.2021.1940675 · Cited by 46
“levels of PD-L2 and CD73.(4) IFN-γ and TNF-α show synergistic activity in regulating many aspects of immunity including production of iNOS(48) IL-6,(49) IL-8 and CXCL-10.”
BackgroundInfluentialZou, R., Jiang, Q., Jin, T., Chen, M., Yao, L., & Ding, H. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.956224 · Cited by 44
“In contrast, CAF-S4 does not exhibit these properties (41).”
BackgroundBright future or blind alley? CAR-T cell therapy for solid tumors
Zhang, K., Chen, H., Li, F., Sheng, H., Chen, F., & Li, Y. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1045024 · Cited by 48
“Among the four subsets, CAF-S1 promotes immunosuppressive environment, which enhances the regulatory T cell capacity to inhibit T effector proliferation (60).”
BackgroundThe impact of hypoxia on tumor-mediated bypassing anti-PD-(L)1 therapy
Mortezaee, K., Majidpoor, J., & Kharazinejad, E. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.114646 · Cited by 45
Wang, D., Wang, N., Li, X., Chen, X., Shen, B., Zhu, D., Zhu, L., Xu, Y., Yu, Y., & Shu, Y. (2021) · Gastric Cancer · doi:10.1007/s10120-021-01175-8 · Cited by 44
Engineering Breast Cancer On-chip—Moving Toward Subtype Specific Models
Moccia, C., & Haase, K. (2021) · Frontiers in Bioengineering and Biotechnology · doi:10.3389/fbioe.2021.694218 · Cited by 49
Zou, T., Lü, W., Mezhuev, Y. O., Lan, M., Li, L., Liu, F., Cai, T., Wu, X. Y., & Cai, Y. (2021) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2021.05.029 · Cited by 44
Role of extracellular matrix architecture and signaling in melanoma therapeutic resistance
Popovic, A., & Tartare‐Deckert, S. (2022) · Frontiers in Oncology · doi:10.3389/fonc.2022.924553 · Cited by 46
The emerging roles of Hedgehog signaling in tumor immune microenvironment
Wang, J., Cui, B., Li, X., Zhao, X., Huang, T., & Ding, X. (2023) · Frontiers in Oncology · doi:10.3389/fonc.2023.1171418 · Cited by 43
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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