Synergistic therapeutic combination with a CAF inhibitor enhances CAR-NK-mediated cytotoxicity via reduction of CAF-released IL-6
Open accessAbstract
Background: Cancer-associated fibroblasts (CAFs) in the tumor microenvironment (TME) contribute to an impaired functionality of natural killer (NK) cells that have emerged as a promising therapeutic modality. The interaction between CAFs and NK cells within the TME exerts major inhibitory effects on immune responses, indicating CAF-targeted therapies as potential targets for effective NK-mediated cancer killing. Methods: To overcome CAF-induced NK dysfunction, we selected an antifibrotic drug, nintedanib, for synergistic therapeutic combination. To evaluate synergistic therapeutic efficacy, we established an in vitro 3D Capan2/patient-derived CAF spheroid model or in vivo mixed Capan2/CAF tumor xenograft model. The molecular mechanism of NK-mediated synergistic therapeutic combination with nintedanib was revealed through in vitro experiments. In vivo therapeutic combination efficacy was subsequently evaluated. Additionally, the expression score of target proteins was measured in patient-derived tumor sections by the immunohistochemical method. Results: Nintedanib blocked the platelet-derived growth factor receptor β (PDGFRβ) signaling pathway and diminished the activation and growth of CAFs, markedly reducing CAF-secreted IL-6. Moreover, coadministration of nintedanib improved the mesothelin (MSLN) targeting chimeric antigen receptor-NK-mediated tumor killing abilities in CAF/tumor spheroids or a xenograft model. The synergistic combination resulted in intense NK infiltration in vivo. Nintedanib alone exerted no effects, whereas blockade of IL-6 trans-signaling ameliorated the function of NK cells. The combination of the expression of MSLN and the PDGFRβ+-CAF population area, a potential prognostic/therapeutic marker, was associated with inferior clinical outcomes. Conclusion: Our strategy against PDGFRβ+-CAF-containing pancreatic cancer allows improvements in the therapy of pancreatic ductal adenocarcinoma.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
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?
Nintedanib can inhibit CAF infiltration.
“It has been reported that nintedanib can inhibit CAF infiltration 50”
From TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance (2025) · cites this paper as [50]
The Results section on MSLN-targeted CAR-NK treatment (page unavailable) reports significantly reduced CAF populations in tumor sections from nintedanib-treated mice. The Results also report fewer CAFs in treated spheroid co-cultures, but attribute that reduction to effects including CAF cell death; the paper does not establish that nintedanib inhibits CAF infiltration into tumors. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Cites
Distinct populations of inflammatory fibroblasts and myofibroblasts in pancreatic cancer
Öhlund, D., Handly-Santana, A., Biffi, G., Elyada, E., Almeida, A. S., Ponz-Sarvise, M., Corbo, V., Oni, T. E., Hearn, S. A., Lee, E. J., et al. (2017) · Journal of Experimental Medicine · doi:10.1084/jem.20162024 · Cited by 2,590 · see citing works
Role of platelet-derived growth factors in physiology and medicinePreprint
Andræ, J., Gallini, R., & Betsholtz, C. (2008) · Genes & Development · doi:10.1101/gad.1653708 · Cited by 2,444 · see citing works
Elyada, 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 · see citing works
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 · see citing works
Kleeff, J., Korc, M., Apte, M., La Vecchia, C., Johnson, C. D., Biankin, A. V., Neale, R. E., Tempero, M., Tuveson, D. A., Hruban, R. H., et al. (2016) · Nature Reviews Disease Primers · doi:10.1038/nrdp.2016.22 · Cited by 1,982 · see citing works
Biffi, G., Oni, T. E., Spielman, B., Hao, Y., Elyada, E., Park, Y., Preall, J., & Tuveson, D. A. (2019) · Cancer Discovery · doi:10.1158/2159-8290.cd-18-0710 · Cited by 1,360 · see citing works
Molecular cloning and expression of an IL-6 signal transducer, gp130
Hibi, M., Murakami, M., Saito, M., Hirano, T., Taga, T., & Kishimoto, T. (1990) · Cell · doi:10.1016/0092-8674(90)90411-7 · Cited by 1,304 · see citing works
NK cells for cancer immunotherapy
Shimasaki, N., Jain, A., & Campana, D. (2020) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0052-1 · Cited by 1,233 · see citing works
Imai, K., Matsuyama, S., Miyaké, S., Suga, K., & Nakachi, K. (2000) · The Lancet · doi:10.1016/s0140-6736(00)03231-1 · Cited by 1,189 · see citing works
Efficacy of a Tyrosine Kinase Inhibitor in Idiopathic Pulmonary Fibrosis
Richeldi, L., Costabel, U., Selman, M., Kim, D. S., Hansell, D. M., Nicholson, A. G., Brown, K. K., Flaherty, K. R., Noble, P. W., Raghu, G., et al. (2011) · New England Journal of Medicine · doi:10.1056/nejmoa1103690 · Cited by 1,157 · see citing works
Suppression of Antitumor Immunity by Stromal Cells Expressing Fibroblast Activation Protein–α
Kraman, M., Bambrough, P. J., Arnold, J. N., Roberts, E. W., Magiera, L., Jones, J. O., Gopinathan, A., Tuveson, D. A., & Fearon, D. T. (2010) · Science · doi:10.1126/science.1195300 · Cited by 1,134 · see citing works
Hyaluronan impairs vascular function and drug delivery in a mouse model of pancreatic cancer
Jacobetz, M. A., Chan, D. S., Neesse, A., Bapiro, T. E., Cook, N., Frese, K. K., Feig, C., Nakagawa, T., Caldwell, M. E., Zecchini, H. I., et al. (2013) · Gut · doi:10.1136/gutjnl-2012-302529 · Cited by 1,120 · see citing works
BIBF 1120: Triple Angiokinase Inhibitor with Sustained Receptor Blockade and Good Antitumor Efficacy
Hilberg, F., Roth, G. J., Krssak, M., Kautschitsch, S., Sommergruber, W., Tontsch-Grunt, U., Garin-Chesa, P., Bader, G., Zoephel, A., Quant, J., et al. (2008) · Cancer Research · doi:10.1158/0008-5472.can-07-6307 · Cited by 1,056 · see citing works
Moncada, R., Barkley, D., Wagner, F., Chiodin, M., Devlin, J. C., Baron, M., Hajdu, C. H., Simeone, D. M., & Yanai, I. (2020) · Nature Biotechnology · doi:10.1038/s41587-019-0392-8 · Cited by 1,045 · see citing works
NKG2D-deficient mice are defective in tumor surveillance in models of spontaneous malignancy
Guerra, N., Tan, Y. X., Joncker, N. T., Choy, A., Gallardo, F., Xiong, N., Knoblaugh, S., Cado, D., Greenberg, N. R., & Raulet, D. H. (2008) · Immunity · doi:10.1016/j.immuni.2008.02.016 · Cited by 850 · see citing works
Loeffler, M. (2006) · Journal of Clinical Investigation · doi:10.1172/jci26532 · Cited by 633 · see citing works
Targeting the PDGF signaling pathway in tumor treatment
Heldin, C. (2013) · Cell Communication and Signaling · doi:10.1186/1478-811x-11-97 · Cited by 541 · see citing works
Stromal Microenvironment Shapes the Intratumoral Architecture of Pancreatic Cancer
Ligorio, M., Sil, S., Malagon-Lopez, J., Nieman, L. T., Misale, S., Pilato, M. D., Ebright, R. Y., Karabacak, M., Kulkarni, A. S., Liu, A., et al. (2018) · Cell · doi:10.1016/j.cell.2019.05.012 · Cited by 534 · see citing works
Tumor-Promoting Desmoplasia Is Disrupted by Depleting FAP-Expressing Stromal Cells
Lo, A., Wang, L.-C. S., Scholler, J., Monslow, J., Avery, D., Newick, K., O'Brien, S., Evans, R. A., Bajor, D. J., Clendenin, C., et al. (2015) · Cancer Research · doi:10.1158/0008-5472.can-14-3041 · Cited by 498 · see citing works
Olivares, O., Mayers, J. R., Gouirand, V., Torrence, M. E., Gicquel, T., Borge, L., Lac, S., Roques, J., Lavaut, M.-N., Berthezène, P., et al. (2017) · Nature Communications · doi:10.1038/ncomms16031 · Cited by 413 · see citing works
Interleukin (IL-6) ImmunotherapyPreprint
Tanaka, T., Narazaki, M., & Kishimoto, T. (2017) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a028456 · Cited by 407 · see citing works
Single-cell analysis defines a pancreatic fibroblast lineage that supports anti-tumor immunity
Hutton, C., Heider, F., Blanco-Gomez, A., Banyard, A., Kononov, A., Zhang, X., Karim, S., Paulus-Hock, V., Watt, D., Steele, N., et al. (2021) · Cancer Cell · doi:10.1016/j.ccell.2021.06.017 · Cited by 337 · see citing works
Hepatocellular carcinoma-associated fibroblasts trigger NK cell dysfunction via PGE2 and IDO
Li, T., Yang, Y., Hua, X., Wang, G., Liu, W., Jia, C., Tai, Y., Zhang, Q., & Chen, G. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.12.020 · Cited by 329 · see citing works
Stromal biology of pancreatic cancer
Chu, G. C., Kimmelman, A. C., Hezel, A. F., & DePinho, R. A. (2007) · Journal of Cellular Biochemistry · doi:10.1002/jcb.21209 · Cited by 321 · see citing works
CAF Subpopulations: A New Reservoir of Stromal Targets in Pancreatic Cancer
Pereira, B., Vennin, C., Papanicolaou, M., Chambers, C. R., Herrmann, D., Morton, J. P., Cox, T. R., & Timpson, P. (2019) · Trends in cancer · doi:10.1016/j.trecan.2019.09.010 · Cited by 309 · see citing works
Hosein, A. N., Huang, H., Wang, Z., Parmar, K., Du, W., Huang, J., Maitra, A., Olson, E., Verma, U., & Brekken, R. A. (2019) · JCI Insight · doi:10.1172/jci.insight.129212 · Cited by 302 · see citing works
Mhaidly, R., & Mechta‐Grigoriou, F. (2021) · Immunological Reviews · doi:10.1111/imr.12978 · Cited by 231 · see citing works
The importance of interventional timing in the bleomycin model of pulmonary fibrosis
Kolb, P., Upagupta, C., Vierhout, M., Ayaub, E. A., Bellaye, P., Gauldie, J., Shimbori, C., Inman, M. D., Ask, K., & Kolb, M. R. J. (2020) · European Respiratory Journal · doi:10.1183/13993003.01105-2019 · Cited by 212 · see citing works
NK cell receptor imbalance and NK cell dysfunction in HBV infection and hepatocellular carcinoma
Sun, C., Sun, H., Zhang, C., & Tian, Z. (2014) · Cellular and Molecular Immunology · doi:10.1038/cmi.2014.91 · Cited by 201 · see citing works
Cancer-Associated Fibroblast (CAF) Heterogeneity and Targeting Therapy of CAFs in Pancreatic Cancer
Geng, X., Chen, H., Zhao, L., Hu, J., Yang, W., Li, G., Cheng, C., Zhao, Z., Zhang, T., Li, L., et al. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2021.655152 · Cited by 188 · see citing works
Reeh, H., Rudolph, N., Billing, U., Christen, H., Streif, S., Bullinger, E., Schliemann-Bullinger, M., Findeisen, R., Schaper, F., Huber, H. J., et al. (2019) · Cell Communication and Signaling · doi:10.1186/s12964-019-0356-0 · Cited by 180 · see citing works
Duperret, E. K., Trautz, A., Ammons, D. T., Perales‐Puchalt, A., Wise, M. C., Yan, J., Reed, C., & Weiner, D. B. (2017) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-17-2033 · Cited by 152 · see citing works
Curti, A., Ruggeri, L., Parisi, S., Bontadini, A., Dan, E., Motta, M. R., Rizzi, S., Trabanelli, S., Očadlíková, D., Lecciso, M., et al. (2016) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-15-1604 · Cited by 139 · see citing works
Metformin attenuates silica-induced pulmonary fibrosis via AMPK signaling
Cheng, D., Xu, Q., Wang, Y., Li, G., Sun, W., Ma, D., Zhou, S., Liu, Y., Han, L., & Ni, C. (2021) · Journal of Translational Medicine · doi:10.1186/s12967-021-03036-5 · Cited by 133 · see citing works
Tejada, M. L., Yu, L., Dong, J., Jung, K., Meng, G., Peale, F. V., Jr., Frantz, G. D., Hall, L., Liang, X., Gerber, H., et al. (2006) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-05-1770 · Cited by 127 · see citing works
Mesothelin as a biomarker for targeted therapy
Lv, J., & Li, P. (2019) · Biomarker Research · doi:10.1186/s40364-019-0169-8 · Cited by 126 · see citing works
Boyd, L. N. C., Andini, K. D., Peters, G. J., Geert Kazemier, M., & Giovannetti, E. (2021) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2021.03.006 · Cited by 113 · see citing works
Determinants and functions of CAFs secretome during cancer progression and therapy
Linares, J., Marín-Jiménez, J. A., Badia-Ramentol, J., & Calon, A. (2021) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2020.621070 · Cited by 110 · see citing works
Einama, T., Kamachi, H., Nishihara, H., Homma, S., Kanno, H., Takahashi, K., Sasaki, A., Tahara, M., 岡田, 邦., Muraoka, S., et al. (2011) · Pancreas · doi:10.1097/mpa.0b013e318221bed8 · Cited by 109 · see citing works
Mesothelin-Targeted Agents in Clinical Trials and in Preclinical Development
Kelly, R. J., Sharon, E., Pastan, I. H., & Hassan, R. (2012) · Molecular Cancer Therapeutics · doi:10.1158/1535-7163.mct-11-0454 · Cited by 102 · see citing works
Targeting TGFβR2‐mutant tumors exposes vulnerabilities to stromal TGFβ blockade in pancreatic cancer
Huang, H., Zhang, Y., Gallegos, V., Sorrelle, N., Zaid, M. M., Toombs, J., Du, W., Wright, S., Hagopian, M., Wang, Z., et al. (2019) · EMBO Molecular Medicine · doi:10.15252/emmm.201910515 · Cited by 87 · see citing works
Li, S., Li, C. R., Pang, X., Zhang, J., Yu, G., Yeo, A. J., Lavin, M. F., Shao, H., Jia, Q., & Peng, C. (2021) · Frontiers in Pharmacology · doi:10.3389/fphar.2021.719589 · Cited by 81 · see citing works
Knops, A. M., South, A., Rodeck, U., Martinez-Outschoorn, U., Harshyne, L., Johnson, J., Luginbuhl, A., & Curry, J. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.565306 · Cited by 76 · see citing works
The Impact of Mesothelin in the Ovarian Cancer Tumor Microenvironment
Hilliard, T. S. (2018) · Cancers · doi:10.3390/cancers10090277 · Cited by 71 · see citing works
PDGF family function and prognostic value in tumor biology
Bartoschek, M., & Pietras, K. (2018) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2018.06.106 · Cited by 64 · see citing works
Cancer-Associated Fibroblasts: Accomplices in the Tumor Immune Evasion
Hilmi, M., Nicolle, R., Bousquet, C., & Neuzillet, C. (2020) · Cancers · doi:10.3390/cancers12102969 · Cited by 64 · see citing works
Activation of somatostatin receptors attenuates pulmonary fibrosis
Borie, R., Fabre, A., Prost, F., Marchal-Sommé, J., Lebtahi, R., Marchand-Adam, S., Aubier, M., Soler, P., & Crestani, B. (2007) · Thorax · doi:10.1136/thx.2007.078006 · Cited by 64 · see citing works
Overexpression of Mesothelin in Pancreatic Ductal Adenocarcinoma (PDAC)
Le, K., Wang, J., Zhang, T., Guo, Y., Chang, H., Wang, S., & Zhu, B. (2020) · International Journal of Medical Sciences · doi:10.7150/ijms.39012 · Cited by 62 · see citing works
PDGF-D−PDGFRβ signaling enhances IL-15–mediated human natural killer cell survival
Ma, S., Tang, T., Wu, X., Mansour, A. G., Lu, T., Zhang, J., Wang, L., Caligiuri, M. A., & Yu, J. (2022) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2114134119 · Cited by 36 · see citing works
Werth, C., Stuhlmann, D., Cat, B., Steinbrenner, H., Alili, L., Sies, H., & Brenneisen, P. (2008) · Carcinogenesis · doi:10.1093/carcin/bgm296 · Cited by 16 · see citing works
Tuğ, T., Kara, H., Karaoğlu, A., Karataş, F., Turgut, N. H., Ayan, E., Boran, Ç., & Tuğ, E. (2012) · Drug and Chemical Toxicology · doi:10.3109/01480545.2012.710618 · Cited by 6 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Gao, 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 53 · see citing works
Breaking the stromal barrier in pancreatic cancer: Advances and challenges
Chakkera, M., Foote, J. B., Farran, B., & Nagaraju, G. P. (2023) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2023.189065 · Cited by 44 · see citing works
Liao, T., Chen, X., Qiu, F., Zhang, X., Wu, F., Zhao, Z., Xu, M., Chen, M., Shen, J., Shen, Q., et al. (2025) · Journal of Nanobiotechnology · doi:10.1186/s12951-025-03217-0 · Cited by 38 · see citing works
Huang, Z., Chen, J., Zhu, T., Li, J., Ng, H. Y., Zhou, Y., Gu, X., Xu, S., & Jia, R. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02533-1 · Cited by 46 · see citing works
Kong, J. C., Sa’ad, M. A., Vijayan, H. M., Ravichandran, M., Balakrishnan, V., Tham, S. K., & Tye, G. J. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1384039 · Cited by 37 · see citing works
Ielpo, S., Barberini, F., Moghaddam, F. D., Pesce, S., Cencioni, C., Spallotta, F., Ninno, A. D., Businaro, L., Marcenaro, E., Bei, R., et al. (2024) · Cancer Treatment Reviews · doi:10.1016/j.ctrv.2024.102843 · Cited by 32 · see citing works
Kim, T. H., Lim, S. H., Lee, H., Chae, Y. C., & Min, D. S. (2026) · Experimental & Molecular Medicine · doi:10.1038/s12276-026-01650-1 · Cited by 33 · see citing works
Self-citationCancer‐Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets
Li, Y., Liu, Q., Jing, X., Wang, Y., Jia, X., Yang, X., & Chen, K. (2025) · MedComm · doi:10.1002/mco2.70292 · Cited by 29 · see citing works
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 · see citing works
Li, B., Zhu, X., Ge, J., Zhang, H., Gao, Y., Bao, X., Dai, X., Du, Z., Tu, X., Zhou, T., et al. (2025) · Molecular Therapy · doi:10.1016/j.ymthe.2025.05.026 · Cited by 26 · see citing works
He, J. N., Gao, Y., Sun, Z., & Liu, S. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1529403 · Cited by 26 · see citing works
Li, X., Li, W., Xu, L., & Song, Y. (2023) · Chinese Medical Journal · doi:10.1097/cm9.0000000000002818 · Cited by 26 · see citing works
Zhang, Z., Tang, Y., Luo, D., Qiu, J. L., & Chen, L. (2025) · APL Bioengineering · doi:10.1063/5.0244706 · Cited by 23 · see citing works
Empowering pancreatic tumor homing with augmented anti-tumor potency of CXCR2-tethered CAR-NK cells
Yoon, J. H., Yoon, H., Kang, H. J., Yoo, H., Choi, M. J., Chung, J.-Y., Seo, M., Kim, M., Lim, S. O., Kim, Y. J., et al. (2024) · Molecular Therapy Oncology · doi:10.1016/j.omton.2024.200777 · Cited by 21 · see citing works
Self-citationZheng, L., Cai, W., Ke, Y., Hu, X., Yang, C., Zhang, R., Wu, H., Liu, D., Yu, H., & Wu, C. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02138-7 · Cited by 21 · see citing works
Tang, H., Cao, Y., Zhou, Y., Ma, Y., Jiang, H., Zhang, H., Jiang, L., Yang, Q.-X., Tang, X.-M., Yang, C. K., et al. (2024) · Journal of Advanced Research · doi:10.1016/j.jare.2024.01.014 · Cited by 20 · see citing works
Shin, S. H., Lee, Y. E., Yoon, H., Yuk, C. M., An, J. Y., Seo, M., Yoon, S. W., Oh, M.-S., Shin, S. C., Kim, J. H., et al. (2024) · Biomaterials · doi:10.1016/j.biomaterials.2024.122888 · Cited by 21 · see citing works
Self-citationPrecision sniper for solid tumors: CAR-NK cell therapy
Li, S., Jing, J., Chen, Y., Chi, E., Wang, B., Xie, Z., Yang, W., Shen, H., & Pan, J. (2025) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-025-04106-z · Cited by 18 · see citing works
Tao, J., Zhang, J., Li, H., Zhou, Y., & Guan, C. (2024) · Critical Reviews in Oncology/Hematology · doi:10.1016/j.critrevonc.2024.104553 · Cited by 14 · see citing works
Inflammation, microbiota, and pancreatic cancer
Chen, X., Sun, F., Wang, X., Feng, X., Aref, A. R., Tian, Y., Ashrafizadeh, M., & Wu, D. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03673-6 · Cited by 13 · see citing works
Chen, H., Xu, X., Li, J., Yu, X. M., Li, X., Zhang, K., Jiang, H., Liu, X., & Li, M. (2024) · Frontiers in Pharmacology · doi:10.3389/fphar.2024.1491400 · Cited by 12 · see citing works
Nanomaterials in cancer immunotherapy: targeting cancer-associated fibroblasts
Zhang, Z., & Chen, L. (2025) · Cancer Nanotechnology · doi:10.1186/s12645-024-00302-1 · Cited by 12 · see citing works
Hydrogel-Based Therapeutics for Pancreatic Ductal Adenocarcinoma Treatment
Liu, J., Wu, W., Zhu, Q., & Zhu, H. (2023) · Pharmaceutics · doi:10.3390/pharmaceutics15102421 · Cited by 11 · see citing works
CAR-T cell technologies that interact with the tumour microenvironment in solid tumours
Taylor, C. A., Glover, M., & Maher, J. F. (2024) · Expert Review of Clinical Immunology · doi:10.1080/1744666x.2024.2380894 · Cited by 12 · see citing works
Cheng, N., Zhou, Q., Jia, Z., Yang, M., Zhang, S., Wang, L., & Chen, Y. (2025) · Materials Today Bio · doi:10.1016/j.mtbio.2024.101441 · Cited by 11 · see citing works
Huang, Y., Liao, H., Luo, J., Wei, H., Li, A., Lu, Y., & Xiang, B. (2025) · Frontiers in Oncology · doi:10.3389/fonc.2024.1502270 · Cited by 10 · see citing works
Design of nano-delivery systems for pancreatic cancer immunotherapy
Fu, S., Gao, C., Yu, Q., Gong, R., Yang, Z., Zang, X., Shan, S., Mombrú, D., Romero, M., Mombrú, Á. W., et al. (2025) · Cancer Letters · doi:10.1016/j.canlet.2025.218098 · Cited by 11 · see citing works
CAR-NK Engineering to Overcome TME Barriers
Islam, F., Pupovac, A., Boyd, R. L., & Trounson, A. O. (2025) · Cells · doi:10.3390/cells15010021 · Cited by 9 · see citing works
Dash, C. P., Sonowal, D., Dhaka, P., Yadav, R., Chettri, D., Satapathy, B. P., Sheoran, P., Uttam, V., Jain, M., & Jain, A. (2024) · Frontiers in Immunology · doi:10.3389/fimmu.2024.1390498 · Cited by 9 · see citing works
TBX3 shapes an immunosuppressive microenvironment and induces immunotherapy resistance
Liu, Z., Zhang, C., Xiao, J., He, Y., Liang, H., Huang, J., Cai, Z., Yi, Z., Chen, M., Li, Y., et al. (2025) · Theranostics · doi:10.7150/thno.103175 · Cited by 8 · see citing works
CAR NK cell therapy for solid tumors: potential and challenges
Yu, Y., & Ho, M. (2025) · Antibody Therapeutics · doi:10.1093/abt/tbaf019 · Cited by 8 · see citing works
Emerging role of cancer-associated fibroblasts in the premetastatic niche
Yang, S., Guo, Y., Jia, J., Cui, W., Zhang, X., Wang, Y., Xie, Z., Fang, Y., Ding, X., Chang, L., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02461-0 · Cited by 8 · see citing works
Peng, Q., Zhang, P., Liu, G., & Lu, L. (2024) · Anti-Cancer Drugs · doi:10.1097/cad.0000000000001651 · Cited by 8 · see citing works
Li, H., Liu, D., Li, K., Wang, Y., Zhang, G., Qi, L., & Xie, K. (2024) · Molecular Medicine Reports · doi:10.3892/mmr.2024.13283 · Cited by 7 · see citing works
Rapid CAR screening and circRNA-driven CAR-NK cells for persistent shed-resistant immunotherapy
Chung, J.-Y., Hong, J., Yee, S., Lim, H. W., Lee, D., Yoon, S.-W., Lee, S.-H., Jung, Y.-J., Shin, S. H., Kim, S. C., et al. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02623-6 · Cited by 5 · see citing works
Self-citationShaping the glioblastoma microenvironment to enhance CAR-NK immunotherapy
Tang, E., & Chen, J. Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1681966 · Cited by 5 · see citing works
Ji, F.-S., Li, H., Wang, Q., Wang, X.-J., Zhang, J.-W., Xiao, Y., Li, H., Liu, H., Long, T.-Q., Wu, B.-Y., et al. (2026) · iMeta · doi:10.1002/imt2.70117 · Cited by 7 · see citing works
Huang, Z., Cong, Z., Luo, J., Qiu, B., Wang, K., Gao, C., Xu, Y., Yang, N., Zou, Z., Hu, L., et al. (2025) · Cancer Cell International · doi:10.1186/s12935-025-03709-x · Cited by 5 · see citing works
Advancing biliary tract malignancy treatment: emerging frontiers in cell-based therapies
Ao, J., Hu, M., Wang, J., & Jiang, X. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1559465 · Cited by 4 · see citing works
NK cell adaptation in the tumor microenvironment: Insights for NK cell-based immunotherapy.
Li, Y., Gao, Y., Wang, L., & Si, J.-W. (2025) · Cytokine & growth factor reviews · doi:10.1016/j.cytogfr.2025.10.003 · Cited by 6 · see citing works
HU, M., Fang, Z., Shao, Y., Yan, J., & Ye, G. H. (2024) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.32604/or.2024.051589 · Cited by 4 · see citing works
Gao, X., Sun, L., Li, T., Li, P., Liu, C., Li, Q., & Zhu, Y. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1647988 · Cited by 3 · see citing works
Yang, J.-P., Kulkarni, N. N., Yamaji, M., Shiraishi, T., Pham, T. Q., Do, H., Aiello, N. M., Shaw, M. H., Nakamura, T., Abiru, A., et al. (2024) · PLoS ONE · doi:10.1371/journal.pone.0314227 · Cited by 3 · see citing works
Zhu, Q., Wei, J., & Han, W. (2025) · Current Issues in Molecular Biology · doi:10.3390/cimb47040249 · Cited by 3 · see citing works
Liu, Z.-N., Yu, L., Liu, P., Liu, H.-Z., Zhao, H., Sun, Y.-Q., Liu, L., Wang, T., Zhang, X., Luo, G., et al. (2025) · Nano Today · doi:10.1016/j.nantod.2025.102877 · Cited by 3 · see citing works
karamivandishi, A., Hatami, A., Eslami, M. M., Soleimani, M., & Izadi, N. (2024) · Human Immunology · doi:10.1016/j.humimm.2024.111207 · Cited by 3 · see citing works
Zu, P., & Yu, Z. (2026) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2026.1761070 · Cited by 2 · see citing works
All-trans retinoic acid and lansoprazole potentiated NKG2D-CAR T for breast cancer treatment
Lu, T., Yu, J., Zhou, R., Zhu, J., Dai, H., & Lv, H. (2026) · International Immunopharmacology · doi:10.1016/j.intimp.2026.116889 · Cited by 2 · see citing works
Gao, H., Qu, L., Li, M., Guan, X., Zhang, S., Deng, X., Wang, J., & Xing, F. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.139829 · Cited by 2 · see citing works
Harnessing the potential of CAR-NK cell therapy in gastrointestinal cancers: From bench to bedside
Vanan, A. G., Askari, M. R., Bagheri, K., Arghand, M. R., Ghorbaninezhad, F., Tahmasebi, S., Taghizadeh-Anvar, M., Nouri, S., & Safarzadeh, E. (2025) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2025.118380 · Cited by 2 · see citing works
Wan, S., Liang, Z., Yao, S., Wang, A., Liu, X., He, H., Cai, H., Gao, Y., & Wang, H. (2024) · Aging · doi:10.18632/aging.205997 · Cited by 2 · see citing works
Chakraborty, S., Durham, C., Bharti, V., Capece, M., Davies, A. E., Vilgelm, A. E., & Skardal, A. (2025) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2025.07.09.662476 · Cited by 2 · see citing works
Kang, S.-B., Jeong, J. H., Kim, S. W., Yoo, H., Lee, S., Oh, J.-H., Sung, C. O., Lee, S.-H., Jun, E., & Jang, M. (2026) · Molecular Therapy Oncology · doi:10.1016/j.omton.2026.201152 · Cited by 1 · see citing works
Self-citationHarnessing the chimeric antigen receptor engineered cells in gastrointestinal cancer immunotherapy
Dadvand, A., Nooroulahi, M., Matin, S., & Faghfuri, E. (2025) · International Immunopharmacology · doi:10.1016/j.intimp.2025.115321
Zhou, X., Fu, C., Fu, Y. J., Jiao, T., Zhao, C., & Yang, D. (2025) · International Journal of Genomics · doi:10.1155/ijog/6004629
Mechanisms and strategies for reversing NK cell exhaustion in tumor immunotherapy
Zhi, L., Wang, Y., Zhao, Z., Guo, Y., Wang, K., He, W., Guo, C., Niu, Z., Zhu, W., & Zhang, X. (2026) · Experimental and Molecular Pathology · doi:10.1016/j.yexmp.2026.105031 · Cited by 1 · see citing works
Suzuki, R., Watanabe, S., Shono, K., MASUDA, T., Yanai, K., Yamazaki, R., Ando, Y., Wakabayashi, T., Tanaka, S., Sekiya, T., et al. (2026) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-026-04350-x
Liu, Y., Zhao, T., Shi, R., Xie, Y., Li, M., & Wang, Y. (2026) · Seminars in Oncology · doi:10.1016/j.seminoncol.2026.152483
Zhang, Z., Rong, W., & Chen, L. (2026) · Journal of Nanobiotechnology · doi:10.1186/s12951-026-04567-z · Cited by 2 · see citing works
Li, Y., Li, Y., Fan, J., San, Z.-Q., & Ye, J. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1900936
Next-generation natural killer cell therapy: bench to bedside and beyond
Zhao, A., Xu, J., Deng, W., Zhang, M., Shao, Y., Liu, Y., Liang, A., Wang, X., Niu, T., & Qian, W. (2026) · Signal Transduction and Targeted Therapy · doi:10.1038/s41392-026-02911-1
- Authors
- Lee, Y. E., Go, G.-Y., Koh, E.-Y., Yoon, H.-N., Seo, M., Hong, S.-M., Jeong, J. H., Kim, J.-C., Cho, D., Kim, T. S., Kim, S. C., Jun, E., & Jang, M.
- Affiliations
- Korea University (KR)
- Korea Institute of Science and Technology (KR)
- Asan Medical Center (KR)
- Corporate Research & Development Center, UCI therapeutics, Seoul, Korea (the Republic of)
- Samsung Medical Center (KR)
- Kyung Hee University (KR)
- Corresponding author
- Kim, Song Cheol
- Jun, Eunsung
- Jang, Mihue
- ORCID
- Venue
- Journal for ImmunoTherapy of Cancer
- Publisher
- BMJ
- Published
- 2023-02
- Volume
- 11
- Issue
- 2
- Pages
- e006130
- ISSN
- 2051-1426 (ISSN-L)
- PMC
- PMC9972461
- OpenAlex
- W4322505517
- Cited by
- 61
- References
- 51
- Citations by year
- 2026: 12 · 2025: 30 · 2024: 15 · 2023: 4
- FWCI
- 6.69
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Journal for ImmunoTherapy of Cancer (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Ministry of Science and ICT, Ministry of Trade, Industry, and Energy, and Ministry of Health and Welfare (RS-2022-00166088)
- Asan Institute for Life Sciences, Asan Medical Center (2021IP0020-1)
- National Research Foundation of Korea (2020M3A9I4038662, 2020M3A9I4038667, 2020R1C1C1006421)
- Samsung Research Funding & Incubation Center of Samsung Electronics (SRFC-TC2003-02)
- Korea Institute of Science and Technology (2E31621, 2V09550)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Cell Function and Interaction
- Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
- Health Sciences › Medicine › Oncology › CAR-T cell therapy research
- Keywords
- cancer-associated fibroblasts, nintedanib, CAR-NK cells, mesothelin, interleukin-6, PDGFRβ signaling, pancreatic ductal adenocarcinoma, tumor microenvironment, NK cell dysfunction, antifibrotic therapy, IL-6 trans-signaling, NK cell infiltration, CAF-targeted therapy
- MeSH terms
- Cancer-Associated Fibroblasts, Receptors, Chimeric Antigen, Humans, Pancreatic Neoplasms, Interleukin-6, 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
