The DOI matches its Crossref record; 44 of the 44 references it cites were found in a registry or an index.
FAP Promotes Immunosuppression by Cancer-Associated Fibroblasts in the Tumor Microenvironment via STAT3–CCL2 Signaling
Published version of a preprint
Abstract
Cancer-associated fibroblasts (CAF) are components of the tumor microenvironment whose contributions to malignant progression are not fully understood. Here, we show that the fibroblast activation protein (FAP) triggers induction of a CAF subset with an inflammatory phenotype directed by STAT3 activation and inflammation-associated expression signature marked by CCL2 upregulation. Enforcing FAP expression in normal fibroblasts was sufficient to endow them with an inflammatory phenotype similar to FAP(+)CAFs. We identified FAP as a persistent activator of fibroblastic STAT3 through a uPAR-dependent FAK-Src-JAK2 signaling pathway. In a murine liver tumor model, we found that FAP(+)CAFs were a major source of CCL2 and that fibroblastic STAT3-CCL2 signaling in this setting promoted tumor growth by enhancing recruitment of myeloid-derived suppressor cells (MDSC). The CCL2 receptor CCR2 was expressed on circulating MDSCs in tumor-bearing subjects and FAP(+)CAF-mediated tumor promotion and MDSC recruitment was abrogated in Ccr2-deficient mice. Clinically, we observed a positive correlation between stromal expression of FAP, p-STAT3, and CCL2 in human intrahepatic cholangiocarcinoma, a highly aggressive liver cancer with dense desmoplastic stroma, where elevated levels of stromal FAP predicted a poor survival outcome. Taken together, our results showed how FAP-STAT3-CCL2 signaling in CAFs was sufficient to program an inflammatory component of the tumor microenvironment, which may hav…
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
“In addition, CAFs secrete substantial amounts of growth factors, proinflammatory cytokines, and chemokines, particularly TGF-β, IL-6, and CC-chemokine ligand 2, which recruit immunosuppressive cells into the tumor stroma and lead to immune escape 20-22.”
From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [21]
Citations
Cites
Mantovani, A., Allavena, P., Sica, A., & Balkwill, F. (2008) · Nature · doi:10.1038/nature07205 · Cited by 11,399
Kalluri, R., & Zeisberg, M. (2006) · Nature Reviews Cancer · doi:10.1038/nrc1877 · Cited by 4,538
STATs in cancer inflammation and immunity: a leading role for STAT3
Yu, H., Pardoll, D., & Jove, R. (2009) · Nature reviews. Cancer · doi:10.1038/nrc2734 · Cited by 4,383
Monocyte Chemoattractant Protein-1 (MCP-1): An Overview
Deshmane, S. L., Kremlev, S., Amini, S., & Sawaya, B. E. (2009) · Journal of Interferon & Cytokine Research · doi:10.1089/jir.2008.0027 · Cited by 3,889
Coordinated regulation of myeloid cells by tumours
Gabrilovich, D. I., Ostrand-Rosenberg, S., & Bronte, V. (2012) · Nature Reviews Immunology · doi:10.1038/nri3175 · Cited by 3,544
Monocyte recruitment during infection and inflammation
Shi, C., & Pamer, E. G. (2011) · Nature Reviews Immunology · doi:10.1038/nri3070 · Cited by 3,015
CCL2 recruits inflammatory monocytes to facilitate breast-tumour metastasis
Qian, B.-Z., Li, J., Zhang, H., Kitamura, T., Zhang, J., Campion, L. R., Kaiser, E. A., Snyder, L. A., & Pollard, J. W. (2011) · Nature · doi:10.1038/nature10138 · Cited by 2,874
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
Feig, C., Jones, J. O., Kraman, M., Wells, R. J. B., Deonarine, A., Chan, D. S., Connell, C. M., Roberts, E. W., Zhao, Q., Caballero, O. L., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1320318110 · Cited by 2,100
Stromal Elements Act to Restrain, Rather Than Support, Pancreatic Ductal Adenocarcinoma
Rhim, A. D., Oberstein, P. E., Thomas, D. H., Mirek, E. T., Palermo, C. F., Sastra, S. A., Dekleva, E. N., Saunders, T., Becerra, C. P., Tattersall, I. W., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.04.021 · Cited by 2,085
Cited by
Sorted by citations
Items 701–757 of 757
An, Y.-Z., Cho, E., Ling, J., & Zhang, X. (2020) · Figshare · doi:10.6084/m9.figshare.13082903
Zhou, S., Yang, K., Chen, S., 练国达, Huang, Y., Yao, H., Zhao, Y., Huang, K., Yin, D., Lin, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26563492
Jiang, J., Xu, C., Han, D., Lu, Y., Yang, F., Wang, J., Yan, X., Mu, X., Zhang, J., Jia, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27124184
陶帮宝, Shi, J., Shuai, S., Zhou, H., Zhang, H., Li, B., Wang, X., Li, G., He, H., & Zhong, J. (2021) · Figshare · doi:10.6084/m9.figshare.15139685
Self-citationQiao, M., Zhou, F., Liu, X., Jiang, T., Wang, H., Li, X., Zhao, C., Cheng, L., Chen, X., Ren, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26674661
Jiang, J., Xu, C., Han, D., Lu, Y., Yang, F., Wang, J., Yan, X., Mu, X., Zhang, J., Jia, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27124178
Qiao, M., Zhou, F., Liu, X., Jiang, T., Wang, H., Li, X., Zhao, C., Cheng, L., Chen, X., Ren, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26674679
Qiao, M., Zhou, F., Liu, X., Jiang, T., Wang, H., Li, X., Zhao, C., Cheng, L., Chen, X., Ren, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26674688
Zhou, S., Yang, K., Chen, S., 练国达, Huang, Y., Yao, H., Zhao, Y., Huang, K., Yin, D., Lin, H., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26563495
An, Y.-Z., Cho, E., Ling, J., & Zhang, X. (2020) · Figshare · doi:10.6084/m9.figshare.13082909
Qiao, M., Zhou, F., Liu, X., Jiang, T., Wang, H., Li, X., Zhao, C., Cheng, L., Chen, X., Ren, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26674667
Shahpar, M. G., Pakravan, K., Razmara, E., Amooie, F., Mahmoudian, M., Heshmati, M., & Babashah, S. (2024) · Figshare · doi:10.6084/m9.figshare.25522689
Song, J., Liu, Q., Han, L., Song, T., Huang, S., Zhang, X., He, Q., Liang, C., Zhu, S., & Xiong, B. (2023) · Figshare · doi:10.6084/m9.figshare.24636488
Jiang, J., Xu, C., Han, D., Lu, Y., Yang, F., Wang, J., Yan, X., Mu, X., Zhang, J., Jia, C., et al. (2024) · Figshare · doi:10.6084/m9.figshare.27124196
Qiao, M., Zhou, F., Liu, X., Jiang, T., Wang, H., Li, X., Zhao, C., Cheng, L., Chen, X., Ren, S., et al. (2024) · Figshare · doi:10.6084/m9.figshare.26674670
Proliferation-cycle gene signatures predict immune landscape and prognosis in lung adenocarcinoma
Lin, C., Zhang, M., Sun, P., He, Y., Tian, Y., Li, W., Pu, S., Luo, J., & Wang, K. (2025) · Discover Oncology · doi:10.1007/s12672-025-04346-6
Wang, N., Xue, S., Li, Z., Cui, J., Dong, B., Liu, Y., Tao, J., Zhu, Z., Fan, Y.-H., Yu, S., et al. (2026) · Asian journal of urology · doi:10.1016/j.ajur.2025.07.003
Xu, Z., Liang, S., You, X., Jin, A., Mao, L., Zhong, F., Yuan, T., He, J., Yi, B., Li, M., et al. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1750890
Molecular features and clinical significance of cancer-associated fibroblasts in colorectal cancer
Yin, Y., Liu, H., Wu, S., Fu, Y., & Peng, S. (2026) · Molecular Biology of the Cell · doi:10.1091/mbc.e25-10-0476 · Cited by 1
Yin, T.-T., Huang, M.-X., Liu, M.-C., Luo, P., Da, T.-T., Huang, C., Yang, P., Yao, Y., & Cao, J. (2026) · Oncogene · doi:10.1038/s41388-026-03686-z
Aseeri, A. A., AlKhafaje, Z., Hussein, U. A.-R., Adel, Z., Alkadir, O. K. A., Aldulaimi, A., Saeed, S. M., Taher, W. M., Alwan, M., & Smerat, A. (2026) · Journal of Pharmaceutical Innovation · doi:10.1007/s12247-026-10504-2
Xue, C. A. I., & Qingfan, H. A. O. (2026) · Cancer Biotherapy and Radiopharmaceuticals · doi:10.1177/10849785261431301
Fibroblastic heterogeneity and metastatic spread in breast cancers
Pelon, F. (2018) · theses.fr (ABES) · doi:10.70675/829dfe15z9dbfz4622za60cz77fac9fc8a96
Ciblage pharmacologique du microenvironnement de l'adénocarcinome canalaire pancréatique
Samain, R. (2018) · theses.fr (ABES) · doi:10.70675/e35639a1z6534z4cb6z9efbza38473efebed
Djerroudi, L., Mhaidly, R., Kieffer, Y., Damei, I., Croizer, H., Selvarasa, V., Gentric, G., Fuhrmann, L., Goncalves, A., Caly, M., et al. (2026) · Nature Communications · doi:10.1038/s41467-026-72844-4
Studies on single domain antibodies VHH against FAPα as potential cancer therapeutics
Sabnani, M. K., Bapat, S., Maheshwari, N. O., & Vyas, R. (2026) · Journal of Biomolecular Structure and Dynamics · doi:10.1080/07391102.2026.2667460
He, T., Zhang, L., & Zhao, Q. (2026) · Hepatoma Research · doi:10.20517/2394-5079.2025.74
Liu, Y., Zhang, Y., Nie, J., Wang, J., Hao, X., & Zhao, L. (2026) · Applied Biochemistry and Biotechnology · doi:10.1007/s12010-026-05721-x
Exner, R. M., Lewis, J. S., Bodei, L., & Pillarsetty, N. (2026) · ACS Pharmacology & Translational Science · doi:10.1021/acsptsci.5c00736
ILDR2 impairs antitumor surveillance by recruiting immunosuppressive CCR2+ monocytes
Nagatomo, Y., Zhang, C., Lu, Y., Widyagarini, A., & Nagai, S. (2026) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2026.154178
Rizk, E. M., Foley, P. A., & Osataphan, S. A. (2026) · Cancers · doi:10.3390/cancers18122001
Zhang, J. C., Yang, Z., He, Z., Qin, L., Tu, Y., Luo, Y., Li, S., Qiu, T., Hong, K., Zhang, X., et al. (2026) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2026.110221
Targeting lysosome-dependent cell death in cancer: towards therapeutic strategies
Li, Y., Feng, J., Dong, X., Yuan, Z., Zheng, L.-L., Zhang, L., & Wang, L. (2026) · Biomarker Research · doi:10.1186/s40364-026-00969-1 · Cited by 1
Three-Dimensional Bioprinting-Enabled Organoids for Engineering the Tumor Microenvironment
Li, Y., Shi, J., Zhang, Q., Huang, H., & Zhou, S. H. E. N. G. H. (2026) · Tissue Engineering Part B Reviews · doi:10.1177/19373368261469463
Reprogramming the vascular-immune niche: Towards a new therapeutic paradigm for glioblastoma
Wen, W., Zhang, Z., Wang, Y., Zhu, G., & Zhang, Q. (2026) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2026.105500
Wang, Y., Jin, X., Wang, H., Zou, J., Yang, H., & Kong, W. (2026) · Journal of Voice · doi:10.1016/j.jvoice.2026.07.012
Targeting Fibroblast Activation Protein for Precision Medicine
Liu, J., Zhao, X., Liu, P., Yu, J., Chen, X. S., & Zhang, J. (2026) · Accounts of Chemical Research · doi:10.1021/acs.accounts.6c00139
Arioka, M., & Takahashi‐Yanaga, F. (2026) · Biochemical Pharmacology · doi:10.1016/j.bcp.2026.118380
Li, J., 阙日升, Zhang, J., Ma, K., Guo, S., Wen, L., Zhao, J., Chen, W., Wang, X., Qin, H., et al. (2026) · Cancer Letters · doi:10.1016/j.canlet.2026.218797
Ismail, M., Al‐Gizey, N., Alabed, Z., Mustafa, N., Al-Najjar, E., Hamdaneh, Y., Eid, N., & Esmail, A. (2026) · Pharmaceuticals · doi:10.3390/ph19091449
Wang, X., Wang, Q., Wang, J., Ding, G., Huang, Y., Feng, Y., & Zou, B. (2026) · Materials Today Advances · doi:10.1016/j.mtadv.2026.100976
Ye, W., Zhong, L., Wang, X., & Chen, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1941227
Ding, K., Yabin, Y., Pu, S., Liu, W., Xie, J., Huang, J., & Luo, Z. (2026) · ACS Sensors · doi:10.1021/acssensors.6c03460
Self-citationLiu, D., Tang, J., Jiang, Y., Zhao, J., Shen, J., You, L., & Zheng, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1979117
Wang, J., Ma, S., Yu, D., Wang, Y., Ma, C., Ma, D., Chang, X., Yang, Y., Jin, M., Wang, Z., et al. (2026) · Journal of Ethnopharmacology · doi:10.1016/j.jep.2026.122561
Molecular advancements in targeting fibroblast activation protein (FAP) in cancer therapies
Talia, M., Scordamaglia, D., Gianì, F., Cirillo, F., Panza, S., Occhiuzzi, M. A., Mondino, A. A., Silvestri, F., Zicarelli, A., Meliti, C., et al. (2026) · Expert Opinion on Therapeutic Targets · doi:10.1080/14728222.2026.2748743
Tu, L., Yi, M., Feng, Z., Wang, Y., Ni, T., Zhou, L., Luo, B., Tang, Y., Ruan, S., Yan, W., et al. (2026) · Journal for ImmunoTherapy of Cancer · doi:10.1136/jitc-2026-016095
Zhan, J., Yan, Z., Cao, Z., Wu, F., Wang, Y., & Zhan, Y. (2026) · Medical Oncology · doi:10.1007/s12032-026-03471-8
BindingDB Entry 50010989: A cell-based fluorescent assay for FAP inhibitor discovery.
BindingDB (2021) · UC San Diego · doi:10.7270/q2n87fc7
Li, J., Zhang, N., Piao, M., Zhao, J., Wang, Y., Li, C., Li, S., Huang, Z., Li, Y., Xun, Z., et al. (2026) · Cancer and Metastasis Reviews · doi:10.1007/s10555-026-10392-5
Self-citationTang, X., Huang, H., 沈小东, Kong, G., Zhang, W., Yu, J., Wu, C., & Wu, J. (2026) · Drug Resistance Updates · doi:10.1016/j.drup.2026.101488
Metadata
- Authors
- Yang, X., Lin, Y., Shi, Y., Li, B., Liu, W., Yin, W., Dang, Y., Chu, Y., Fan, J., & He, R.
- Affiliations
- Shanghai Medical College of Fudan University (CN)
- Venue
- Cancer Research
- Published
- 2016-07-14
- Volume
- 76
- Issue
- 14
- Pages
- 4124-4135
- ISSN
- 0008-5472 (ISSN-L)
- 1538-7445
- OpenAlex
- W2400022769
- Cited by
- 748
- References
- 44
- Citations by year
- 2026: 66 · 2025: 101 · 2024: 107 · 2023: 115 · 2022: 91 · 2021: 95 · 2020: 67 · 2019: 47 · 2018: 31 · 2017: 25 · 2016: 3
- FWCI
- 19.03
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Cancer Research (publishedVersion)
- PubMed (publishedVersion)
- Funders
- NSFC (813220437, 81471555, 81272389)
- National Key Sci-Tech Project (2012ZX10002011-002)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Peptidase Inhibition and Analysis
- 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
- fibroblast activation protein, cancer-associated fibroblasts, tumor microenvironment, STAT3 signaling, MCP-1, CCR2, myeloid-derived suppressor cells, uPAR, desmoplasia, intrahepatic cholangiocarcinoma, liver cancer, immunosuppression, tumor stroma
- MeSH terms
- Cancer-Associated Fibroblasts, Fibroblast Activation Protein Alpha, Animals, Cell Movement, Female, Immune Tolerance, Membrane Proteins, Mice, Inbred C57BL, Endopeptidases, Serine Endopeptidases, Signal Transduction, Gelatinases, Chemokine CCL2, STAT3 Transcription Factor, Mice, Focal Adhesion Protein-Tyrosine Kinases, Janus Kinase 2, Receptors, Urokinase Plasminogen Activator, 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
