STAT3, a master regulator of anti-tumor immune response

Rébé, Cédric; Ghiringhelli, François

doi:10.3390/cancers11091280

Cited by 130Cytokine Signaling Pathways and InteractionsCancer Immunotherapy and BiomarkersT-cell and B-cell Immunology

STAT3, a master regulator of anti-tumor immune response

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Rébé, Cédric, Ghiringhelli, François·2019·Cancers

DOI 10.3390/cancers11091280PMC PMC6770459

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Abstract

Immune cells in the tumor microenvironment regulate cancer growth. Thus cancer progression is dependent on the activation or repression of transcription programs involved in the proliferation/activation of lymphoid and myeloid cells. One of the main transcription factors involved in many of these pathways is the signal transducer and activator of transcription 3 (STAT3). In this review we will focus on the role of STAT3 and its regulation, e.g., by phosphorylation or acetylation in immune cells and how it might impact immune cell function and tumor progression. Moreover, we will review the ability of STAT3 to regulate checkpoint inhibitors.

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IL-6 is a key factor in inflammation, autoimmunity and cancer, with its effect mainly exerted through the IL-6-STAT3 pathway.
“IL-6 is also a key factor in inflammation, autoimmunity and cancer, with its effect mainly exerted through the IL-6–signal transducer and activator of transcription 3 (STAT3) pathway (18–26, 61–65).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [25]
Section 3.2 (Dendritic Cells; page not available) describes IL-6 acting through gp130–STAT3 in immune-cell differentiation, and Section 3.1 (Macrophages) links IL-6/STAT3 signaling to pro-tumor effects. Section 2.2 (Th17) links IL-6-induced cells to autoimmune disorders. These passages support roles for IL-6 in the named contexts, but do not establish that its effects across inflammation, autoimmunity, and cancer are mainly exerted through STAT3. (LLM, conf=0.84)
Experimental — accuracy not yet measured
NF-κB and STAT3 play crucial roles in cancer development and progression.
“Furthermore, NF-κB and STAT3 play crucial roles in cancer development and progression (19, 25, 67, 279).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [25]
The Introduction describes STAT3 signaling as a major pathway driving cellular transformation, proliferation, invasion and metastasis in cancer. Section 4 mentions NF-κB as involved in PD-L1 expression in melanoma, but does not establish the broader claim that NF-κB plays a crucial role in cancer development and progression generally. No page numbers are available in our copy. (LLM, conf=0.85)
Experimental — accuracy not yet measured
Other inhibitors against the IL-6-STAT3 signaling pathway are under development.
“Other inhibitors against the IL-6–STAT3 signaling pathway are under development (19, 21, 24–26, 76, 374).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [25]
The Conclusions (section 5; page unavailable) identify direct STAT3 inhibitors and indirect approaches that block IL-6 or JAK2 signaling, and discuss the complexity of clinical development. They do not clearly state that other IL-6–STAT3 inhibitors are currently under development. (LLM, conf=0.78)
Experimental — accuracy not yet measured
STAT3 functions as an inhibitor for dendritic cell differentiation, maturation and antigen-presenting ability, and therefore STAT3 inhibits tumor immunity by interfering with dendritic cell functions.
“Much evidence has accumulated to show that STAT3 functions as an inhibitor for DC differentiation, maturation and antigen-presenting ability, and therefore STAT3 inhibits tumor immunity by interfering with DC functions (Fig. 2) (25).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [25]
Myeloid-derived suppressor cell function is dependent on STAT3.
“MDSC function is dependent on STAT3 (25).”
From IL-6 in inflammation, autoimmunity and cancer (2021) · cites this paper as [25]

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Glioblastoma-Derived IL6 Induces Immunosuppressive Peripheral Myeloid Cell PD-L1 and Promotes Tumor Growth
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Breast Cancer-Derived Exosomes Alter Macrophage Polarization via gp130/STAT3 Signaling
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Dendritic cells are the principal cells in mouse spleen bearing immunogenic fragments of foreign proteins.
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Positive and Negative Transcriptional Regulation of the Foxp3 Gene is Mediated by Access and Binding of the Smad3 Protein to Enhancer I
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FGFR2 Promotes Expression of PD-L1 in Colorectal Cancer via the JAK/STAT3 Signaling Pathway
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Immune Checkpoint Inhibitor Combinations in Solid Tumors: Opportunities and Challenges
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EML4-ALK enhances programmed cell death-ligand 1 expression in pulmonary adenocarcinoma via hypoxia-inducible factor (HIF)-1α and STAT3
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Corosolic acid inhibits glioblastoma cell proliferation by suppressing the activation of signal transducer and activator of transcription‐3 and nuclear factor‐kappa B in tumor cells and tumor‐associated macrophages
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Plasminogen activator inhibitor-1 promotes the recruitment and polarization of macrophages in cancer
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Combined analysis of p53 and vascular endothelial growth factor expression in colorectal carcinoma for determination of tumor vascularity and liver metastasis
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Targeting Stat3 in the Myeloid Compartment Drastically Improves the In vivo Antitumor Functions of Adoptively Transferred T Cells
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STAT3 inhibition induces Bax-dependent apoptosis in liver tumor myeloid-derived suppressor cells
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Ibrutinib modulates the immunosuppressive CLL microenvironment through STAT3-mediated suppression of regulatory B-cell function and inhibition of the PD-1/PD-L1 pathway
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AKT-STAT3 Pathway as a Downstream Target of EGFR Signaling to Regulate PD-L1 Expression on NSCLC cells
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IL-6 down-regulates HLA class II expression and IL-12 production of human dendritic cells to impair activation of antigen-specific CD4+ T cells
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Lysyl Oxidase 3 Is a Dual-Specificity Enzyme Involved in STAT3 Deacetylation and Deacetylimination Modulation
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Interferon-α Up-Regulates the Expression of PD-L1 Molecules on Immune Cells Through STAT3 and p38 Signaling
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A novel role for histone deacetylase 6 in the regulation of the tolerogenic STAT3/IL-10 pathway in APCs
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Myeloid ERK5 deficiency suppresses tumor growth by blocking protumor macrophage polarization via STAT3 inhibition
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Enhanced Cancer Immunotherapy Using STAT3-Depleted Dendritic Cells with High Th1-Inducing Ability and Resistance to Cancer Cell-Derived Inhibitory Factors
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STAT3 in CD8+ T Cells Inhibits Their Tumor Accumulation by Downregulating CXCR3/CXCL10 Axis
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S1PR1 Is Crucial for Accumulation of Regulatory T Cells in Tumors via STAT3
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Insights Into the Molecular Mechanisms of T Follicular Helper-Mediated Immunity and Pathology
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TH9 cells in anti-tumor immunity
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BMP-6 in Renal Cell Carcinoma Promotes Tumor Proliferation through IL-10–Dependent M2 Polarization of Tumor-Associated Macrophages
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Dendritic cells with an increased PD-L1 by TGF-β induce T cell anergy for the cytotoxicity of hepatocellular carcinoma cells
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STAT3 Inhibition Combined with CpG Immunostimulation Activates Antitumor Immunity to Eradicate Genetically Distinct Castration-Resistant Prostate Cancers
Moreira, D., Adamus, T., Zhao, X., Su, Y.-L., Zhang, Z., White, S. V., Swiderski, P., Lu, X., DePinho, R. A., Pal, S. K., et al. (2018) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-18-1277 · Cited by 80 · see citing works
PD-L1 up-regulation restrains Th17 cell differentiation in STAT3 loss- and STAT1 gain-of-function patients
Zhang, Y., Ma, C. A., Lawrence, M. G., Break, T. J., O’Connell, M. P., Lyons, J. J., López, D., Barber, J. S., Zhao, Y., Barber, D. L., et al. (2017) · The Journal of Experimental Medicine · doi:10.1084/jem.20161427 · Cited by 78 · see citing works
STAT3 Is Indispensable to IL-27-Mediated Cell Proliferation but Not to IL-27-Induced Th1 Differentiation and Suppression of Proinflammatory Cytokine Production
Owaki, T., Asakawa, M., Morishima, N., Mizoguchi, I., Fukai, F., Takeda, K., Mizuguchi, J., & Yoshimoto, T. (2008) · The Journal of Immunology · doi:10.4049/jimmunol.180.5.2903 · Cited by 77 · see citing works
Gene-based strategies for the immunotherapy of cancer
Tüting, T., Storkus, W. J., & Lotze, M. T. (1997) · Journal of Molecular Medicine · doi:10.1007/s001090050133 · Cited by 76 · see citing works
Inhibiting signal transducer and activator of transcription 3: rationality and rationale design of inhibitors
Mankan, A. K., & Greten, F. R. (2011) · Expert Opinion on Investigational Drugs · doi:10.1517/13543784.2011.601739 · Cited by 75 · see citing works
Polarization of Tissue-Resident TFH-Like Cells in Human Hepatoma Bridges Innate Monocyte Inflammation and M2b Macrophage Polarization
Chen, M., Xiao, C., Lao, X., Yuan, W., Liu, R., Zeng, Q., Wang, J., Ouyang, F., Chen, D., Chan, K., et al. (2016) · Cancer Discovery · doi:10.1158/2159-8290.cd-16-0329 · Cited by 74 · see citing works
Nucleus, mitochondrion, or reticulum? STAT3 à La Carte
Avalle, L., & Poli, V. (2018) · International Journal of Molecular Sciences · doi:10.3390/ijms19092820 · Cited by 74 · see citing works
Suppression of SOCS3 in macrophages prevents cancer metastasis by modifying macrophage phase and MCP2/CCL8 induction
Hiwatashi, K., Tamiya, T., Hasegawa, E., Fukaya, T., Hashimoto, M., Kakoi, K., Kashiwagi, I., Kimura, A., Inoue, N., Morita, R., et al. (2011) · Cancer Letters · doi:10.1016/j.canlet.2011.04.024 · Cited by 73 · see citing works
Development of T follicular helper cells and their role in disease and immune system
Eivazi, S., Bagheri, S., Hashemzadeh, M. S., Ghalavand, M., Qamsari, E. S., Dorostkar, R., & Yasemi, M. (2016) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2016.10.083 · Cited by 72 · see citing works
Tumor stroma-derived factors skew monocyte to dendritic cell differentiation toward a suppressive CD14+PD-L1+phenotype in prostate cancer
Spary, L. K., Salimu, J., Webber, J. P., Clayton, A., Mason, M. D., & Tabi, Z. (2014) · OncoImmunology · doi:10.4161/21624011.2014.955331 · Cited by 71 · see citing works
Epigenetic activation during T helper 17 cell differentiation is mediated by Tripartite motif containing 28
Jiang, Y., Liu, Y., Li, J., Sun, S., Jin, W., Wang, X., & Dong, C. (2018) · Nature Communications · doi:10.1038/s41467-018-03852-2 · Cited by 67 · see citing works
Overexpression of Indoleamine 2,3-Dioxygenase 1 Promotes Epithelial-Mesenchymal Transition by Activation of the IL-6/STAT3/PD-L1 Pathway in Bladder Cancer
Zhang, W., Zhang, J., Zhang, Z., Guo, Y., Wu, Y., Wang, R., Wang, L., Mao, S., & Yao, X. (2018) · Translational Oncology · doi:10.1016/j.tranon.2018.11.012 · Cited by 65 · see citing works
Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy
Verdeil, G., Lawrence, T., Schmitt‐Verhulst, A., & Auphan‐Anezin, N. (2019) · Cancers · doi:10.3390/cancers11121832 · Cited by 63 · see citing works
STAT heterodimers in immunity
Delgoffe, G. M., & Vignali, D. (2013) · JAK-STAT · doi:10.4161/jkst.23060 · Cited by 62 · see citing works
STAT3 inhibition specifically in human monocytes and macrophages by CD163-targeted corosolic acid-containing liposomes
Andersen, M. N., Etzerodt, A., Graversen, J. H., Holthof, L. C., Moestrup, S. K., Hokland, M., & Møller, H. J. (2019) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-019-02301-3 · Cited by 61 · see citing works
SOCS3 Deficiency in Myeloid Cells Promotes Tumor Development: Involvement of STAT3 Activation and Myeloid-Derived Suppressor Cells
Yu, H., Liu, Y., McFarland, B. C., Deshane, J. S., Hurst, D. R., Ponnazhagan, S., Benveniste, E. N., & Qin, H. (2015) · Cancer Immunology Research · doi:10.1158/2326-6066.cir-15-0004 · Cited by 60 · see citing works
ROCK2, but not ROCK1 interacts with phosphorylated STAT3 and co-occupies TH17/TFH gene promoters in TH17-activated human T cells
Chen, W., Nyuydzefe, M. S., Weiss, J. M., Zhang, J., Waksal, S. D., & Zanin‐Zhorov, A. (2018) · Scientific Reports · doi:10.1038/s41598-018-35109-9 · Cited by 58 · see citing works
An oligonucleotide decoy for Stat3 activates the immune response of macrophages to breast cancer
Sun, Z., Yao, Z., Liu, S., Tang, H., & Xiong, Y. (2006) · Immunobiology · doi:10.1016/j.imbio.2005.11.004 · Cited by 57 · see citing works
SOCS3 Transactivation by PPARγ Prevents IL-17–Driven Cancer Growth
Berger, H., Végran, F., Chikh, M., Gilardi, F., Ladoire, S., Bugaut, H., Mignot, G., Chalmin, F., Bruchard, M., Dérangère, V., et al. (2013) · Cancer Research · doi:10.1158/0008-5472.can-12-4018 · Cited by 55 · see citing works
Self-citation
Integrated STAT3 and Ikaros Zinc Finger Transcription Factor Activities Regulate Bcl-6 Expression in CD4+ Th Cells
Read, K. A., Powell, M. D., Baker, C. E., Sreekumar, B. K. N., Ringel-Scaia, V. M., Bachus, H., Martin, R. E., Cooley, I. D., Allen, I. C., Ballesteros‐Tato, A., et al. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1700106 · Cited by 53 · see citing works
Role of the HDAC6/STAT3 pathway in regulating PD-L1 expression in osteosarcoma cell lines
Keremu, A., Aimaiti, A., Liang, Z., & Zou, X. (2018) · Cancer Chemotherapy and Pharmacology · doi:10.1007/s00280-018-3721-6 · Cited by 53 · see citing works
Tumor-Induced STAT3 Signaling in Myeloid Cells Impairs Dendritic Cell Generation by Decreasing PKCβII Abundance
Farren, M. R., Carlson, L. M., Netherby, C. S., Lindner, I., Li, P., Gabrilovich, D. I., Abrams, S. I., & Lee, K. P. (2014) · Science Signaling · doi:10.1126/scisignal.2004656 · Cited by 51 · see citing works
MiR-125a-5p Decreases the Sensitivity of Treg cells Toward IL-6-Mediated Conversion by Inhibiting IL-6R and STAT3 Expression
Li, D., Kong, C., Tsun, A., Chen, C., Song, H., Shi, G., Pan, W. Q., Dai, D., Shen, N., & Li, B. (2015) · Scientific Reports · doi:10.1038/srep14615 · Cited by 51 · see citing works
The ERBB-STAT3 Axis Drives Tasmanian Devil Facial Tumor Disease
Kosack, L., Wingelhofer, B., Popa, A., Orlova, A., Agerer, B., Vilagos, B., Májek, P., Parapatics, K., Lercher, A., Ringler, A., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2018.11.018 · Cited by 50 · see citing works
CD163 as a novel target gene of STAT3 is a potential therapeutic target for gastric cancer
Cheng, Z., Zhang, D., Gong, B., Wang, P., & Liu, F. (2017) · Oncotarget · doi:10.18632/oncotarget.20244 · Cited by 50 · see citing works
STAT3 Impairs STAT5 Activation in the Development of IL-9–Secreting T Cells
Olson, M. R., Verdan, F. F., Hufford, M. M., Dent, A. L., & Kaplan, M. H. (2016) · The Journal of Immunology · doi:10.4049/jimmunol.1501801 · Cited by 48 · see citing works
Regulation of immunophenotype modulation of monocytes-macrophages from M1 into M2 by prostate cancer cell-culture supernatant via transcription factor STAT3
Solís-Martínez, R., Cancino-Marentes, M., Hernández-Flores, G., Ortiz-Lazareno, P., Mandujano-Álvarez, G., Cruz-Gálvez, C., Sierra-Díaz, E., Rodríguez-Padilla, C., Jave-Suárez, L. F., Aguilar-Lemarroy, A., et al. (2018) · Immunology Letters · doi:10.1016/j.imlet.2018.02.009 · Cited by 47 · see citing works
Importance of CD4+ Helper T-cells in Antitumor Immunity
Shiku, H. (2003) · International Journal of Hematology · doi:10.1007/bf02986610 · Cited by 43 · see citing works
p38 Mitogen-Activated Protein Kinase/Signal Transducer and Activator of Transcription-3 Pathway Signaling Regulates Expression of Inhibitory Molecules in T Cells Activated by HIV-1-Exposed Dendritic Cells
Che, K. F., Shankar, E. M., Muthu, S., Zandi, S., Sigvardsson, M., Hinkula, J., Messmer, D., & Larsson, M. (2012) · Molecular Medicine · doi:10.2119/molmed.2012.00103 · Cited by 43 · see citing works
Imbalanced gp130-Dependent Signaling in Macrophages Alters Macrophage Colony-Stimulating Factor Responsiveness via Regulation of c-fms Expression
Jenkins, B. J., Grail, D., Inglese, M., Quilici, C., Bozinovski, S., Wong, P., & Ernst, M. (2004) · Molecular and Cellular Biology · doi:10.1128/mcb.24.4.1453-1463.2004 · Cited by 43 · see citing works
Anti-cancer versus cancer-promoting effects of the interleukin-17-producing T helper cells
Hemdan, N. Y. A. (2012) · Immunology Letters · doi:10.1016/j.imlet.2012.11.002 · Cited by 42 · see citing works
An Inhibitory Role for the Transcription Factor Stat3 in Controlling IL-4 and Bcl6 Expression in Follicular Helper T Cells
Wu, H., Xu, L., Teuscher, P., Liu, H., Kaplan, M. H., & Dent, A. L. (2015) · The Journal of Immunology · doi:10.4049/jimmunol.1500335 · Cited by 40 · see citing works
Antigen-presenting cell-derived IL-6 restricts the expression of GATA3 and IL-4 by follicular helper T cells
Hercor, M., Anciaux, M., Denanglaire, S., Debuisson, D., Léo, O., & Andris, F. (2016) · Journal of Leukocyte Biology · doi:10.1189/jlb.1hi1115-511r · Cited by 37 · see citing works
STAT3 regulates cytotoxicity of human CD57+ CD4+ T cells in blood and lymphoid follicles
Alshekaili, J., Chand, R., Lee, C. E., Corley, S., Kwong, K., Papa, I., Fulcher, D. A., Randall, K. L., Leiding, J. W., Ma, C. S., et al. (2018) · Scientific Reports · doi:10.1038/s41598-018-21389-8 · Cited by 37 · see citing works
The tyrosine phosphatase SHP-1 dampens murine Th17 development.
Mauldin, I., Tung, K., & Lorenz, U. (2012) · Blood · doi:10.1182/blood-2011-09-377069 · Cited by 35 · see citing works
A Jak2-selective inhibitor potently reverses the immune suppression by modulating the tumor microenvironment for cancer immunotherapy
He, W., Zhu, Y., Mu, R., Xu, J., Zhang, X., Wang, C., Li, Q., Huang, Z. D., Zhang, J., Pan, Y., et al. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.08.019 · Cited by 34 · see citing works
Cyclin-dependent kinase 5 represses Foxp3 gene expression and Treg development through specific phosphorylation of Stat3 at Serine 727
Lam, E., Choi, S. H., Pareek, T. K., Kim, B.-G., & Letterio, J. J. (2015) · Molecular Immunology · doi:10.1016/j.molimm.2015.06.015 · Cited by 32 · see citing works
Embelin impairs the accumulation and activation of MDSCs in colitis-associated tumorigenesis
Wu, T., Wang, C., Wang, W., Hui, Y., Zhang, R., Qiao, L., & Dai, Y. (2018) · OncoImmunology · doi:10.1080/2162402x.2018.1498437 · Cited by 29 · see citing works
Platelet Factor 4 Inhibits IL-17/Stat3 Pathway via Upregulation of SOCS3 Expression in Melanoma
Fang, S., Liu, B., Sun, Q., Zhao, J., Qi, H., & Li, Q. (2014) · Inflammation · doi:10.1007/s10753-014-9903-4 · Cited by 27 · see citing works
Epigenetic Component p66a Modulates Myeloid-Derived Suppressor Cells by Modifying STAT3
Xin, J., Zhang, Z., Su, X., Wang, L., Zhang, Y., & Yang, R. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601712 · Cited by 27 · see citing works
STAT3 Activation Impairs the Stability of Th9 Cells
Ulrich, B. J., Verdan, F. F., McKenzie, A. N. J., Kaplan, M. H., & Olson, M. R. (2017) · The Journal of Immunology · doi:10.4049/jimmunol.1601624 · Cited by 26 · see citing works
Regulation of NKG2D+CD8+T-cell-mediated antitumor immune surveillance: Identification of a novel CD28 activation-mediated, STAT3 phosphorylation-dependent mechanism
Hu, J., Batth, I. S., Xia, X., & Li, S. (2016) · OncoImmunology · doi:10.1080/2162402x.2016.1252012 · Cited by 26 · see citing works
Bypassing STAT3-mediated inhibition of the transcriptional regulator ID2 improves the antitumor efficacy of dendritic cells
Li, H. S., Liu, C., Xiao, Y., Chu, F., Liang, X., Peng, W., Hu, J., Neelapu, S. S., Sun, S., Hwu, P., et al. (2016) · Science Signaling · doi:10.1126/scisignal.aaf3957 · Cited by 22 · see citing works
The differentiation and plasticity of Tc17 cells are regulated by CTLA-4-mediated effects on STATs
Arra, A., Lingel, H., Kuropka, B., Pick, J., Schnoeder, T. M., Fischer, T., Freund, C., Pierau, M., & Brunner-Weinzierl, M. C. (2017) · OncoImmunology · doi:10.1080/2162402x.2016.1273300 · Cited by 22 · see citing works
The Cooperative Relationship between STAT5 and Reactive Oxygen Species in Leukemia: Mechanism and Therapeutic Potential
Mi, T., Wang, Z., & Bunting, K. D. (2018) · Cancers · doi:10.3390/cancers10100359 · Cited by 22 · see citing works
JAK1/STAT3 activation directly inhibits IL-12 production in dendritic cells by preventing CDK9/P-TEFb recruitment to the p35 promoter
Wagner, A. H., Conzelmann, M., Fitzer, F., Giese, T., Gülow, K., Falk, C. S., Krämer, O. H., Dietrich, S., Hecker, M., & Luft, T. (2015) · Biochemical Pharmacology · doi:10.1016/j.bcp.2015.04.019 · Cited by 21 · see citing works
PM01183 Inhibits Myeloid-Derived Suppressor Cells In Vitro and In Vivo
Kuroda, H., Mabuchi, S., Kozasa, K., Yokoi, E., Matsumoto, Y., Komura, N., Kawano, M., Hashimoto, K., Sawada, K., & Kimura, T. (2017) · Immunotherapy · doi:10.2217/imt-2017-0046 · Cited by 19 · see citing works
Enhanced CD8 T cell cross-presentation by macrophages with targeted disruption of STAT3
Brayer, J. B., Cheng, F., Wang, H., Horna, P., Vicente-Suarez, I., Pinilla-Ibarz, J. A., & Sotomayor, E. M. (2010) · Immunology Letters · doi:10.1016/j.imlet.2010.03.004 · Cited by 19 · see citing works
High‐dose wogonin exacerbates DSS ‐induced colitis by up‐regulating effector T cell function and inhibiting Treg cell
Xiao, W., Yin, M., Wu, K., Lu, G., Deng, B., Zhang, Y., Li, Q., Jia, X., Ding, Y., & Gong, W. (2016) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12964 · Cited by 19 · see citing works
Human TH9 differentiation is dependent on signal transducer and activator of transcription (STAT) 3 to restrain STAT1-mediated inhibition
Zhang, Y., Siegel, A., Sun, G., DiMaggio, T., Freeman, A. F., & Milner, J. D. (2018) · Journal of Allergy and Clinical Immunology · doi:10.1016/j.jaci.2018.06.036 · Cited by 18 · see citing works
Docetaxel Down-Regulates PD-1 Expression via STAT3 in T Lymphocytes
Zhang, C., Li, F., Li, J., Xu, Y., Wang, L., & Zhang, Y. (2018) · Clinical Lung Cancer · doi:10.1016/j.cllc.2018.04.010 · Cited by 16 · see citing works
Novel Checkpoints and Cosignaling Molecules in Cancer Immunotherapy
Giuroiu, I., & Weber, J. S. (2017) · The Cancer Journal · doi:10.1097/ppo.0000000000000241 · Cited by 15 · see citing works
Aberrant expression of p-STAT3 in peripheral blood CD4+ and CD8+ T cells related to hepatocellular carcinoma development
Wang, X., XIN, W., Zhang, H., Zhang, F., GAO, M., Yuan, L., Xu, X., Hu, X., & Zhao, M. (2014) · Molecular Medicine Reports · doi:10.3892/mmr.2014.2510 · Cited by 14 · see citing works
STAT3-silenced human dendritic cells have an enhanced ability to prime IFNγ production by both αβ and γδ T lymphocytes
Sanseverino, I., Purificato, C., Varano, B., Conti, L., Gessani, S., & Gauzzi, M. C. (2014) · Immunobiology · doi:10.1016/j.imbio.2014.02.012 · Cited by 13 · see citing works

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Sorted by citations

IL-6 in inflammation, autoimmunity and cancer
Hirano, T. (2021) · International Immunology · doi:10.1093/intimm/dxaa078 · Cited by 1,453 · see citing works
“Furthermore, NF-κ B and STAT3 play crucial roles in cancer development and progression (19, 25, 67, 279).”
BackgroundInfluential
Targeting STAT3 in Cancer Immunotherapy
Zou, S., Tong, Q., Liu, B., Huang, W., Tian, Y., & Fu, X. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01258-7 · Cited by 1,075 · see citing works
Therapy resistance: opportunities created by adaptive responses to targeted therapies in cancer
Labrie, M., Brugge, J. S., Mills, G. B., & Zervantonakis, I. K. (2022) · Nature reviews. Cancer · doi:10.1038/s41568-022-00454-5 · Cited by 388 · see citing works
Immunotherapy efficacy on mismatch repair-deficient colorectal cancer: From bench to bedside
Lizardo, D. Y., Kuang, C., Hao, S., Yu, J., Huang, Y., & Zhang, L. (2020) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2020.188447 · Cited by 212 · see citing works
Microalgae with Immunomodulatory Activities
Riccio, G., & Lauritano, C. (2019) · Marine Drugs · doi:10.3390/md18010002 · Cited by 186 · see citing works
The pleiotropic role of transcription factor STAT3 in oncogenesis and its targeting through natural products for cancer prevention and therapy
Garg, M., Shanmugam, M. K., Bhardwaj, V., Goel, A., Gupta, R., Sharma, A., Baligar, P., Kumar, A. P., Goh, B. C., Wang, L., et al. (2020) · Medicinal Research Reviews · doi:10.1002/med.21761 · Cited by 142 · see citing works
Biomarker-directed targeted therapy plus durvalumab in advanced non-small-cell lung cancer: a phase 2 umbrella trial
Besse, B., Tostivint, E. P., Park, K., Hartl, S., Forde, P. M., Hochmair, M. J., Awad, M. M., Thomas, M., Goss, G. D., Wheatley‐Price, P., et al. (2024) · Nature Medicine · doi:10.1038/s41591-024-02808-y · Cited by 140 · see citing works
Novel activators and small-molecule inhibitors of STAT3 in cancer
Yang, L., Lin, S., Xu, L., Lin, J., Zhao, C., & Huang, X. (2019) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2019.10.005 · Cited by 121 · see citing works
Pivotal Role of STAT3 in Shaping Glioblastoma Immune Microenvironment
Piperi, C., Papavassiliou, K. A., & Papavassiliou, A. G. (2019) · Cells · doi:10.3390/cells8111398 · Cited by 119 · see citing works
Targeting STAT3 Signaling Pathway in Colorectal Cancer
Gargalionis, A. N., Papavassiliou, K. A., & Papavassiliou, A. G. (2021) · Biomedicines · doi:10.3390/biomedicines9081016 · Cited by 113 · see citing works
Icaritin‐induced immunomodulatory efficacy in advanced hepatitis B virus‐related hepatocellular carcinoma: Immunodynamic biomarkers and overall survival
Qin, S., Li, Q., Xu, J., Liang, J., Cheng, Y., Fan, Y., Jiang, J., Ye, H., Tao, H., Li, L., et al. (2020) · Cancer Science · doi:10.1111/cas.14641 · Cited by 92 · see citing works
STAT3 blockade ameliorates LPS-induced kidney injury through macrophage-driven inflammation
Lee, S. H., Kim, K. H., Lee, S. M., Park, S., Lee, S., Cha, R., Lee, J. W., Kim, D. K., Kim, Y. S., Ye, S., et al. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01841-1 · Cited by 85 · see citing works
RETRACTED: Codelivery of STAT3 and PD-L1 siRNA by hyaluronate-TAT trimethyl/thiolated chitosan nanoparticles suppresses cancer progression in tumor-bearing mice
Bastaki, S., Surendar, A., Saheb, N. A., Kashani, M. A., Dorofeev, A. E., Kiani, F. K., Jahandideh, H., Dargani, F. B., Aksoun, M., Nikkhoo, A., et al. (2020) · Life Sciences · doi:10.1016/j.lfs.2020.118847 · Cited by 84 · see citing works
Retracted
Multicellular Effects of STAT3 in Non-small Cell Lung Cancer: Mechanistic Insights and Therapeutic Opportunities
Parakh, S., Ernst, M., & Poh, A. R. (2021) · Cancers · doi:10.3390/cancers13246228 · Cited by 76 · see citing works
Mechanism of Bazhen decoction in the treatment of colorectal cancer based on network pharmacology, molecular docking, and experimental validation
Lu, S., Sun, X., Zhou, Z., Tang, H., Xiao, R., Lv, Q., Wang, B., Qu, J., Yu, J., Sun, F., et al. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1235575 · Cited by 66 · see citing works
Targeting STAT3 and STAT5 in Tumor-Associated Immune Cells to Improve Immunotherapy
Verdeil, G., Lawrence, T., Schmitt‐Verhulst, A., & Auphan‐Anezin, N. (2019) · Cancers · doi:10.3390/cancers11121832 · Cited by 63 · see citing works
Rational Design of Suprastat: A Novel Selective Histone Deacetylase 6 Inhibitor with the Ability to Potentiate Immunotherapy in Melanoma Models
Noonepalle, S. K. R., Shen, S., Ptáček, J., Tavares, M. T., Zhang, G., Stránský, J., Pavlı́ček, J., Ferreira, G. M., Hadley, M. M., Pelaez, G. D., et al. (2020) · Journal of Medicinal Chemistry · doi:10.1021/acs.jmedchem.0c00567 · Cited by 61 · see citing works
Inhibiting STAT3 signaling pathway by natural products for cancer prevention and therapy: In vitro and in vivo activity and mechanisms of action
Yang, J., Wang, L., Guan, X., & Qin, J. (2022) · Pharmacological Research · doi:10.1016/j.phrs.2022.106357 · Cited by 61 · see citing works
STAT3/miR-135b/NF-κB axis confers aggressiveness and unfavorable prognosis in non-small-cell lung cancer
Zhao, J., Wang, X., Mi, Z., Jiang, X., Sun, L., Zheng, B., Wang, J., Meng, M., Zhang, L., Wang, Z., et al. (2021) · Cell Death and Disease · doi:10.1038/s41419-021-03773-x · Cited by 59 · see citing works
Hypoxia-driven protease legumain promotes immunosuppression in glioblastoma
Pang, L., Guo, S., Khan, F., Dunterman, M., Ali, H. A., Liu, Y., Huang, Y.-Y., & Chen, P. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101238 · Cited by 58 · see citing works
Inflammatory Networks in Renal Cell Carcinoma
Kruk, L., Mamtimin, M., Braun, A., Anders, H., Andrassy, J., Gudermann, T. W., & Mammadova‐Bach, E. (2023) · Cancers · doi:10.3390/cancers15082212 · Cited by 57 · see citing works
Targeting the STAT3 oncogenic pathway: Cancer immunotherapy and drug repurposing
Dong, Y., Chen, J., Chen, Y., & Liu, S. (2023) · Biomedicine & Pharmacotherapy · doi:10.1016/j.biopha.2023.115513 · Cited by 54 · see citing works
Tumor-Associated Macrophages in Glioblastoma: Mechanisms of Tumor Progression and Therapeutic Strategies
Chen, J., Wu, Q., Berglund, A., Macaulay, R. J. B., Mulé, J. J., & Etame, A. B. (2025) · Cells · doi:10.3390/cells14181458 · Cited by 49 · see citing works
Tumor-Derived Extracellular Vesicles Enable Tumor Tropism Chemo-Genetherapy for Local Immune Activation in Triple-Negative Breast Cancer
Peng, Z., Zhao, T., Gao, P., Zhang, G., Wu, X., Tian, H., Qu, M., Tan, X., Zhang, Y., Zhao, X., et al. (2024) · ACS Nano · doi:10.1021/acsnano.3c12967 · Cited by 46 · see citing works
STAT3: A key signaling molecule for converting cold to hot tumors
Hu, R., Han, Q., & Zhang, J. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.05.035 · Cited by 45 · see citing works
Breast cancer tumor microenvironment affects Treg/IL-17-producing Treg/Th17 cell axis: Molecular and therapeutic perspectives
Seif, F., Torki, Z., Zalpoor, H., Habibi, M., & Pornour, M. (2023) · Molecular Therapy — Oncolytics · doi:10.1016/j.omto.2023.01.001 · Cited by 42 · see citing works
The complex network of transcription factors, immune checkpoint inhibitors and stemness features in colorectal cancer: A recent update
Merhi, M., Ahmad, F., Taib, N., Inchakalody, V. P., Shahab Uddin, M. S., Shablak, A., & Dermime, S. (2023) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2023.01.001 · Cited by 41 · see citing works
Renal cancer: signaling pathways and advances in targeted therapies
Jiang, A., Li, J., He, Z., Liu, Y., Qiao, K., Fang, Y., Qu, L., Luo, P., Lin, A., & Wang, L. (2024) · MedComm · doi:10.1002/mco2.676 · Cited by 41 · see citing works
Transcriptional Regulation of Cancer Immune Checkpoints: Emerging Strategies for Immunotherapy
Venkatraman, S., Meller, J., Hongeng, S., Tohtong, R., & Chutipongtanate, S. (2020) · Vaccines · doi:10.3390/vaccines8040735 · Cited by 37 · see citing works
STAT3 and mutp53 Engage a Positive Feedback Loop Involving HSP90 and the Mevalonate Pathway
Romeo, M. A., Montani, M. S. G., Benedetti, R., Santarelli, R., D’Orazi, G., & Cirone, M. (2020) · Frontiers in Oncology · doi:10.3389/fonc.2020.01102 · Cited by 36 · see citing works
Overcoming Acquired Drug Resistance to Cancer Therapies through Targeted STAT3 Inhibition
Singh, S., Gomez, H. J., Thakkar, S., Singh, S. P., & Parihar, A. S. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24054722 · Cited by 38 · see citing works
Inhibition of STAT3 augments antitumor efficacy of anti-CTLA-4 treatment against prostate cancer
Witt, K., Axelsson, S. E., Lundqvist, A., Johansson, M., Bjartell, A. S., & Hellsten, R. (2021) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-021-02915-6 · Cited by 35 · see citing works
EZH2 Exacerbates Breast Cancer by Methylating and Activating STAT3 Directly
Zhao, Y., Hu, Z., Li, J., & Hu, T. (2021) · Journal of Cancer · doi:10.7150/jca.50675 · Cited by 35 · see citing works
Coordinated regulation of immune contexture: crosstalk between STAT3 and immune cells during breast cancer progression
Jin, J., Li, Y., Zhao, Q.-J., Chen, Y., Fu, S., & Wu, J.-B. (2021) · Cell communication and signaling : CCS · doi:10.1186/s12964-021-00705-2 · Cited by 31 · see citing works
RNAi mediated silencing of STAT3/PD-L1 in tumor-associated immune cells induces robust anti-tumor effects in immunotherapy resistant tumors
Ganesh, S., Kim, M. J., Lee, J., Feng, X., Ule, K., Mahan, A. L., Krishnan, H. S., Wang, Z., Anzahaee, M. Y., Singhal, G., et al. (2024) · Molecular Therapy · doi:10.1016/j.ymthe.2024.03.035 · Cited by 31 · see citing works
2′-Hydroxycinnamaldehyde ameliorates imiquimod-induced psoriasiform inflammation by targeting PKM2-STAT3 signaling in mice
Hao, L., Mao, Y., Park, J., Kwon, B., Bae, E. J., & Park, B. (2021) · Experimental & Molecular Medicine · doi:10.1038/s12276-021-00620-z · Cited by 27 · see citing works
Emphasis on Adipocyte Transformation: Anti-Inflammatory Agents to Prevent the Development of Cancer-Associated Adipocytes
Na, H., Song, Y., & Lee, H. (2023) · Cancers · doi:10.3390/cancers15020502 · Cited by 26 · see citing works
STAT1 and STAT3 Exhibit a Crosstalk and Are Associated with Increased Inflammation in Hepatocellular Carcinoma
Ploeger, C., Schreck, J., Huth, T., Fraas, A., Albrecht, T., Charbel, A., Ji, J., Singer, S., Breuhahn, K., Pusch, S., et al. (2022) · Cancers · doi:10.3390/cancers14051154 · Cited by 23 · see citing works
Inhibition of STAT3/PD-L1 and Activation of miR193a-5p Are Critically Involved in Apoptotic Effect of Compound K in Prostate Cancer Cells
Lee, J.-H., Lee, D., Lee, H., Im, E., Sim, D. Y., Park, J.-E., Park, W.-Y., Shim, B., & Kim, S. (2021) · Cells · doi:10.3390/cells10082151 · Cited by 21 · see citing works
RETRACTED ARTICLE: Discovery of novel benzohydroxamate-based histone deacetylase 6 (HDAC6) inhibitors with the ability to potentiate anti-PD-L1 immunotherapy in melanoma
Peng, X., Yu, Z., Surineni, G., Deng, B., Zhang, M., Li, C., Sun, Z., Pan, W., Liu, Y., Liu, S., et al. (2023) · Journal of Enzyme Inhibition and Medicinal Chemistry · doi:10.1080/14756366.2023.2201408 · Cited by 21 · see citing works
Retracted
Induction of immunogenic cell death and enhancement of the radiation-induced immunogenicity by chrysin in melanoma cancer cells
Jafari, S., Ardakan, A. K., Aghdam, E. M., Mesbahi, A., Montazersaheb, S., & Molavi, O. (2024) · Scientific Reports · doi:10.1038/s41598-024-72697-1 · Cited by 20 · see citing works
p53-regulated SESN1 and SESN2 regulate cell proliferation and cell death through control of STAT3
Haidurov, A., Zheltukhin, A. O., Snezhkina, A. V., Krasnov, G. S., Kudryavtseva, A. V., & Budanov, A. V. (2025) · Cell Communication and Signaling · doi:10.1186/s12964-025-02104-3 · Cited by 20 · see citing works
Design, Synthesis, and Biological Evaluation of Novel Quinazolin-4(3H)-one-Based Histone Deacetylase 6 (HDAC6) Inhibitors for Anticancer Activity
Khetmalis, Y. M., Fathima, A., Schweipert, M., Debarnot, C., Bandaru, N. V. M. R., Murugesan, S., Trinath, J., Meyer‐Almes, F., & Sekhar, K. V. G. C. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms241311044 · Cited by 18 · see citing works
The cross-talk between STAT1/STAT3 and ROS up-regulates PD-L1 and promotes the release of pro-inflammatory/immune suppressive cytokines in primary monocytes infected by HHV-6B
Romeo, M. A., Montani, M. S. G., Benedetti, R., Giambelli, L., D’Aprile, R., Gaeta, A., Faggioni, A., & Cirone, M. (2020) · Virus Research · doi:10.1016/j.virusres.2020.198231 · Cited by 18 · see citing works
Myeloid-derived suppressor cells and regulatory T cells in colorectal cancer: a synergistic immunosuppressive axis and emerging therapeutic opportunities
Zhang, W., Jin, C., Liu, S., Wan, X., Li, Y., Liu, J., Duan, Z., Ma, J., & Gao, Y. (2026) · Frontiers in Immunology · doi:10.3389/fimmu.2026.1757513 · Cited by 22 · see citing works
Targeting STAT3 and STAT5 in Cancer
de Araujo, E. D., Keserű, G. M., Gunning, P. T., & Moriggl, R. (2020) · Cancers · doi:10.3390/cancers12082002 · Cited by 17 · see citing works
A STAT3/integrin axis accelerates pancreatic cancer initiation and progression
Campos, A. D., Shepard, R. M., Ortega, Z. M., Heumann, I., Wilke, A. E., Nam, A., Cable, C., Kouhmareh, K., Klemke, R., Mattson, N. M., et al. (2025) · Cell Reports · doi:10.1016/j.celrep.2025.116010 · Cited by 16 · see citing works
Mechanism of Action of Melatonin as a Potential Adjuvant Therapy in Inflammatory Bowel Disease and Colorectal Cancer
Jurjus, A. R., Masri, J. E., Ghazi, M., Ayoubi, L. M. E., Soueid, L., Geagea, A. G., & Jurjus, R. A. (2024) · Nutrients · doi:10.3390/nu16081236 · Cited by 16 · see citing works
TLR4 and pSTAT3 Expression on Circulating Tumor Cells (CTCs) and Immune Cells in the Peripheral Blood of Breast Cancer Patients: Prognostic Implications
Papadaki, M. A., Monastirioti, A. A., Apostolopoulou, C. A., Aggouraki, D., Papadaki, C., Michaelidou, K., Vassilakopoulou, M., Alexakou, K., Mavroudis, D., & Agelaki, S. (2022) · Cancers · doi:10.3390/cancers14041053 · Cited by 16 · see citing works
Coagulation Protease-Driven Cancer Immune Evasion: Potential Targets for Cancer Immunotherapy
Paul, S., Mukherjee, T., & Das, K. (2024) · Cancers · doi:10.3390/cancers16081568 · Cited by 15 · see citing works
Chuanxiong Rhizoma regulates ferroptosis and the immune microenvironment in ischemic stroke through the JAK-STAT3 pathway
Ge, Q., Wang, Z., Yu, J., Feng, X., Li, J., Zhang, X., Wang, S., Wang, L., & Chen, Y. (2024) · Scientific Reports · doi:10.1038/s41598-024-82486-5 · Cited by 15 · see citing works
Efficient polymeric nanoparticles for RNAi in macrophage reveal complex effects on polarization markers upon knockdown of STAT3/STAT6
Walther, M., Jenke, R., Aigner, A. M., & Ewe, A. (2024) · European Journal of Pharmaceutics and Biopharmaceutics · doi:10.1016/j.ejpb.2024.114232 · Cited by 14 · see citing works
Nature's Arsenal: Harnessing the Capacity of Phytochemicals to Enhance Immune Checkpoint Inhibitor Therapy of Cancers: An Especial Attention to Brain Malignancies.
Afshari, A.-R., Sanati, M., Ahmadi, S. S., Kesharwani, P., & Sahebkar, A. (2024) · Cancer Letters · doi:10.1016/j.canlet.2024.216955 · Cited by 15 · see citing works
Th17 cells in cancer: plasticity‐driven immunopathology and therapeutic opportunity
Sutanto, H., Ningtyas, M. C., Rachma, B., Pratiwi, L., & Fetarayani, D. (2025) · Immunology and Cell Biology · doi:10.1111/imcb.70043 · Cited by 14 · see citing works
8‐Epi ‐xanthatin induces the apoptosis of DU145 prostate carcinoma cells through signal transducer and activator of transcription 3 inhibition and reactive oxygen species generation
Lee, Y., Choi, J., Yoon, Y. J., Sim, Y., Ryu, H. W., Oh, S., Kim, D., Hwang, J.-H., Chi, S., Han, D. C., et al. (2020) · Phytotherapy Research · doi:10.1002/ptr.6918 · Cited by 12 · see citing works
STAT3 Polymorphism Associates With mTOR Inhibitor-Induced Interstitial Lung Disease in Patients With Renal Cell Carcinoma
Yamamoto, K., Ioroi, T., Shinomiya, K., Yoshida, A., Harada, K., Fujisawa, M., Omura, T., Ikemi, Y., Nakagawa, S., Yonezawa, A., et al. (2022) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.3727/096504022x16418911579334 · Cited by 10 · see citing works
Paracrine Regulation and Immune System Pathways in the Inflammatory Tumor Microenvironment of Lung Cancer: Insights into Oncogenesis and Immunotherapeutic Strategies
Batrash, F., Shaik, A., Rauf, R., Kutmah, M., & Zhang, J. (2024) · Cancers · doi:10.3390/cancers16061113 · Cited by 11 · see citing works
Inhibition of STAT3: A promising approach to enhancing the efficacy of chemotherapy in medulloblastoma
Kumar, S., Arwind, D. A., Harish Kumar., B., Pandey, S., Nayak, R., Vithalkar, M. P., Kumar, N., & Pai, K. S. R. (2024) · Translational Oncology · doi:10.1016/j.tranon.2024.102023 · Cited by 10 · see citing works
Glucocorticoid Receptor-Targeted Nanoliposome for STAT3 Inhibition-Led Myeloid-Derived Suppressor Cell Modulation and Efficient Colon Cancer Treatment
Bhattacharyya, T., Das, P., Ansari, A., Mohan, A. A., Chandra, Y., Narayan, K. P., & Banerjee‬‬‬‬‬‬‬‬‬, R. (2025) · ACS Applied Bio Materials · doi:10.1021/acsabm.5c00002 · Cited by 10 · see citing works
IL-17 induces NSCLC cell migration and invasion by elevating MMP19 gene transcription and expression through the interaction of p300-dependent STAT3-K631 acetylation and its Y705-phosphorylation
GE, W., Li, Y., RUAN, Y., Wu, N., Ma, P., Xu, T., Shu, Y., WANG, Y., Qiu, W., & Zhao, C. (2024) · Oncology Research Featuring Preclinical and Clinical Cancer Therapeutics · doi:10.32604/or.2023.031053 · Cited by 10 · see citing works
Methylgerambullin Derived From Plant Glyccsmis Pentaphylla (Retz) Correa. Mediates Anti-Hepatocellular Carcinoma Cancer Effect by Activating Mitochondrial and Endoplasmic Reticulum Stress Signaling and Inhibiting AKT and STAT3 Pathways.
Wu, C., Shu, G.-W., Huang, H.-Q., Pang, K., Yang, X.-Z., & Yang, G.-Z. (2021) · Food and Chemical Toxicology · doi:10.1016/j.fct.2021.112031 · Cited by 9 · see citing works
Intratumoural expression of IL-6/STAT3, IL-17 and FOXP3 immune cells in the immunosuppressive tumour microenvironment of colorectal cancerImmune cells-positive for IL-6, STAT3, IL-17 and FOXP3 and colorectal cancer development
Gulubova, M. V., Chonov, D. C., Ivanova, K. V., Hristova, M. K., Krasimirova-Ignatova, M. M., & Vlaykova, T. I. (2022) · Biotechnology & Biotechnological Equipment · doi:10.1080/13102818.2022.2072765 · Cited by 10 · see citing works
STAT activation in regulatory CD4+ T cells of patients with primary sclerosing cholangitis
Dold, L., Kalthoff, S., Frank, L., Zhou, T., Esser, P. L., Lutz, P. L., Strassburg, C. P., Spengler, U., & Langhans, B. (2024) · Immunity Inflammation and Disease · doi:10.1002/iid3.1248 · Cited by 9 · see citing works
At the Crossroads of Molecular Biology and Immunology: Molecular Pathways for Immunological Targeting of Head and Neck Squamous Cell Carcinoma
Wondergem, N. E., Nijenhuis, D. N. L. M., Poell, J. B., Leemans, C. R., Brakenhoff, R. H., & van de Ven, R. (2021) · Frontiers in Oral Health · doi:10.3389/froh.2021.647980 · Cited by 9 · see citing works
Interferon-γ-mediated selective inhibition of hematopoiesis and the clonal advantage of HLA-lacking hematopoietic stem progenitor cells in aplastic anemia
Takahashi, R., Takahashi, H., Seoka, L., Iwasaki, H., Takamatsu, H., Imi, T., Zaimoku, Y., Hosokawa, K. T., & Katagiri, T. (2025) · Leukemia · doi:10.1038/s41375-025-02595-6 · Cited by 8 · see citing works
Potential value and mechanism of Rosa roxburghii tratt juice on pro-inflammatory responses in peripheral blood of patients with arsenic poisoning
Dong, L., Xia, S., Sun, B., Ma, L., Chen, X., Wei, S., Zou, Z., & Zhang, A. (2022) · Human & Experimental Toxicology · doi:10.1177/09603271221121313 · Cited by 8 · see citing works
Transcriptional Control of Regulatory T Cells in Cancer: Toward Therapeutic Targeting?
Stéphan, P., Lautraite, R., Voisin, A., & Grinberg‐Bleyer, Y. (2020) · Cancers · doi:10.3390/cancers12113194 · Cited by 8 · see citing works
IKBKE, a prognostic factor preferentially expressed in mesenchymal glioblastoma, modulates tumoral immunosuppression through the STAT3/PD‐L1 pathway
Li, Y., Guo, G., Li, J., Fan, X., Li, T., Tong, L., Liu, P., Wang, X., Yuan, F., Yu, S., et al. (2020) · Clinical and Translational Medicine · doi:10.1002/ctm2.130 · Cited by 7 · see citing works
Epstein-Barr virus infectious particles initiate B cell transformation and modulate cytokine response
Baccianti, F., Masson, C., Delécluse, S., Li, Z., Poirey, R., & Delecluse, H. (2023) · mBio · doi:10.1128/mbio.01784-23 · Cited by 7 · see citing works
A network pharmacology approach to elucidate the anti-inflammatory and antioxidant effects of bitter leaf (Vernonia amygdalina Del.)
Sailah, I., Tallei, T. E., Safitri, L., Tamala, Y., Halimatushadyah, E., Ekatanti, D., Maulydia, N. B., & Çeli̇k, İ. (2024) · Narra J · doi:10.52225/narra.v4i3.1016 · Cited by 8 · see citing works
Esketamine attenuates traumatic brain injury by modulating STAT3-mediated Glycolysis and immune responses
Liu, Y., Gong, Z., Zhang, L., Yang, X., Zhu, J., Zhou, X., & Liao, X. (2025) · BMC Neuroscience · doi:10.1186/s12868-025-00941-z · Cited by 7 · see citing works
A cohort study using IL-6/Stat3 activity and PD-1/PD-L1 expression to predict five-year survival for patients after gastric cancer resection
Li, X. N., Peng, Y. H., Yue, W., Lin, T., & Zhang, W. J. (2022) · PLoS ONE · doi:10.1371/journal.pone.0277908 · Cited by 7 · see citing works
Antitumor Activity of the Cardiac Glycoside αlDiginoside by Modulating Mcl-1 in Human Oral Squamous Cell Carcinoma Cells
Weng, J., Lin, W., Bai, L., Hu, J., & Feng, C. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21217947 · Cited by 7 · see citing works
Prostate cancer immunotherapy-based strategies: an updated review emphasizing immune checkpoint inhibitors
Lu, H., Teng, Z., Wang, J., & Zhang, W. (2025) · Frontiers in Immunology · doi:10.3389/fimmu.2025.1583363 · Cited by 7 · see citing works
Comprehensive Genomic and Transcriptomic Analysis of Three Synchronous Primary Tumours and a Recurrence from a Head and Neck Cancer Patient
Bresadola, L., Weber, D., Ritzel, C., Löwer, M., Bukur, V., Akilli‐Öztürk, Ö., Becker, J., Mehanna, H. M., Schrörs, B., Vascotto, F., et al. (2021) · International Journal of Molecular Sciences · doi:10.3390/ijms22147583 · Cited by 6 · see citing works
Companion Animals as Models for Inhibition of STAT3 and STAT5
Kieslinger, M., Swoboda, A., Kramer, N., Pratscher, B., Wolfesberger, B., & Burgener, I. A. (2019) · Cancers · doi:10.3390/cancers11122035 · Cited by 6 · see citing works
A New IL-6-Inducing Mechanism in Cancer with New Therapeutic Possibilities
Håkansson, L., Dunér, P., Broströmer, E., Gustavsson, B. G., Wettergren, Y., Ghafouri, B., Håkansson, A., & Clinchy, B. (2024) · Cancers · doi:10.3390/cancers16213588 · Cited by 5 · see citing works
VPS35/Retromer-dependent MT1-MMP regulation confers melanoma metastasis
Hao, Q., Bai, Y., Guan, R., Dong, R., Bai, W., Hamdy, H., Wang, L., Meng, M., Sun, Y., Shen, J., et al. (2025) · Science China Life Sciences · doi:10.1007/s11427-024-2884-2 · Cited by 5 · see citing works
The missing link? LGMN connects hypoxia and immunosuppression in glioblastoma
Mitchell, J., Colon, B., Bayık, D., & Lathia, J. D. (2023) · Cell Reports Medicine · doi:10.1016/j.xcrm.2023.101293 · Cited by 5 · see citing works
Using bioinformatics and artificial intelligence to map the cyclin-dependent kinase 4/6 inhibitor biomarker landscape in breast cancer
Wager, K., Wang, Y., Liew, A. T. F., Campbell, D., Liu, F., Martini, J.-F., Ziaee, N., & Liu, Y. (2024) · Future Oncology · doi:10.1080/14796694.2024.2419352 · Cited by 5 · see citing works
Targeting STAT3 pathway: A promising immunotherapeutic strategy for triple-negative breast cancer – Current status and future outlooks
Malekinejad, Z., Aghdam, E. M., Ardakan, A. K., Forghan, E., Alizadeh, M., Simiyari, R., Heidari, H. R., & Montazersaheb, S. (2025) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2025.178079 · Cited by 6 · see citing works
Immune Subtype Profiling and Establishment of Prognostic Immune-Related lncRNA Pairs in Human Ovarian Cancer
Wang, X., Wang, J., & Yu, M. (2022) · Computational and Mathematical Methods in Medicine · doi:10.1155/2022/8338137 · Cited by 5 · see citing works
Retracted
Nifuroxazide in combination with CpG ODN exerts greater efficacy against hepatocellular carcinoma
Wang, Y., Liu, W., Liu, M., Wang, H., Zhou, L., Chen, J., Sun, H. X., Wei, X., Fan, M., Yang, M., et al. (2022) · International Immunopharmacology · doi:10.1016/j.intimp.2022.108911 · Cited by 5 · see citing works
Discovery of selective HDAC6 inhibitors capped by flavonoid or flavonoid-analogous moieties as anti-cancer therapeutics simultaneously harboring anti-proliferative and immunomodulatory activities
He, G., Li, Z., Zhang, M., Li, Z., Wang, Y., Zhao, F., Wang, Y., & Ma, X. (2022) · Bioorganic Chemistry · doi:10.1016/j.bioorg.2022.106146 · Cited by 5 · see citing works
Multifaceted roles for STAT3 in gammaherpesvirus latency revealed through in vivo B cell knockout models
Hogan, C. H., Owens, S. M., Reynoso, G. V., Liao, Y., Meyer, T. J., Zelazowska, M. A., Liu, B., Li, X., Großkopf, A. K., Khairallah, C. F., et al. (2024) · mBio · doi:10.1128/mbio.02998-23 · Cited by 5 · see citing works
Immune Evasion in Cancer Is Regulated by Tumor-Asociated Macrophages (TAMs): Targeting TAMs
Jung, M., & Bonavida, B. (2024) · Critical Reviews™ in Oncogenesis · doi:10.1615/critrevoncog.2024053096 · Cited by 5 · see citing works
Stat3 Regulates Developmental Hematopoiesis and Impacts Myeloid Cell Function via Canonical and Non-Canonical Modalities
Sobah, M. L., Liongue, C., & Ward, A. C. (2024) · Journal of Innate Immunity · doi:10.1159/000538364 · Cited by 5 · see citing works
Preliminary preclinical study of Chol-DsiRNA polyplexes formed with PLL[30]-PEG[5K] for the RNAi-based therapy of breast cancer
Ye, Z., Abdelmoaty, M. M., Ambardekar, V. V., Curran, S. M., Dyavar, S. R., Arnold, L. L., Cohen, S. M., Kumar, D., Alnouti, Y., Coulter, D. W., et al. (2021) · Nanomedicine Nanotechnology Biology and Medicine · doi:10.1016/j.nano.2021.102363 · Cited by 5 · see citing works
B cell-intrinsic STAT3-mediated support of latency and interferon suppression during murine gammaherpesvirus 68 infection revealed through an in vivo competition modelPreprint
Hogan, C. H., Owens, S. M., Reynoso, G. V., Kirillov, V., Meyer, T. J., Zelazowska, M. A., Liu, B., Li, X., Chikhalya, A., Dong, Q., et al. (2023) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/2023.03.22.533727 · Cited by 5 · see citing works
A novel immunological perspective on female-specific cancers: Exploring the signaling pathways of tertiary lymphoid structures and their clinical applications
Li, S., Zhu, X., Liu, Y.-Y., & Chen, M. (2025) · Life Sciences · doi:10.1016/j.lfs.2025.123800 · Cited by 4 · see citing works
The Significance of STAT3 in Colonic Diseases: A Comprehensive Study of Pathological Roles and Therapeutic Implications
Ahmed, A. T., Oghenemaro, E. F., Hjazi, A., Jain, V. D., Ahmad, I., Roopashree, R., Soothwal, P. K., Goswami, M., Zwamel, A. H., & Kdhim, K. (2025) · Cell Biochemistry and Biophysics · doi:10.1007/s12013-025-01816-0 · Cited by 4 · see citing works
Combined therapeutic effect of YHO-1701 with PD-1 blockade is dependent on natural killer cell activity in syngeneic mouse models
Takahashi, H., Miyoshi, N., Murakami, H., Okamura, Y., Ogo, N., Takagi, A., Muraoka, D., & Asai, A. (2023) · Cancer Immunology Immunotherapy · doi:10.1007/s00262-023-03440-4 · Cited by 4 · see citing works
The PAR-score based on PANoptosis genes predicts the progression of ulcerative colitis and the response to anti-TNF-α treatment
Li, Y., Yin, X., Shi, Z., Zhao, Y. L., & Zhong, X. (2025) · Genes & Genomics · doi:10.1007/s13258-025-01675-2 · Cited by 3 · see citing works
Antioxidant and Immunoprotective Effects of Moroccan Honey, Bee Pollen, and Propolis Against Cyclophosphamide‐Induced Immunosuppression in Mice: In Vitro, In Vivo, and In Silico Insights
El-Yagoubi, K., Ouassete, M. E., Soulo, N., Aouji, M., Touzani, S., & Lyoussi, B. (2026) · Journal of Food Science · doi:10.1111/1750-3841.70877 · Cited by 3 · see citing works
Combination of STAT3 inhibitor with Herceptin reduced immune checkpoints expression and provoked anti‐breast cancer immunity: An in vitro study
Jahangiri, A., Ezzeddini, R., Kermani, N. Z., Bahrami, F., & Farrokhi, A. S. (2023) · Scandinavian Journal of Immunology · doi:10.1111/sji.13300 · Cited by 3 · see citing works
MicroRNA-135b mainly functions as an oncogene during tumor progression
Ghasaban, F. T., Taghehchian, N., Zangouei, A. S., Keivany, M. R., & Moghbeli, M. (2024) · Pathology - Research and Practice · doi:10.1016/j.prp.2024.155547 · Cited by 3 · see citing works
Pan-cancer analysis of STAT3 indicates its potential prognostic value and correlation with immune cell infiltration in prostate cancer
Tuo, Z., Zhang, H., He, K., Jiang, Z., Jiang, C., Chen, X., & Yuan, H. (2024) · Discover Oncology · doi:10.1007/s12672-024-01527-7 · Cited by 3 · see citing works
RNA drugs and nonviral nanocarriers in oncology – present status and emerging concepts
Aigner, A. M. (2025) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2025.152512 · Cited by 3 · see citing works
B7H6 silencing increases chemosensitivity to dacarbazine and suppresses cell survival and migration in cutaneous melanoma
Mohammadi, A., Najafi, S., Amini, M. A., Baradaran, B., & Firouzamandi, M. (2023) · Melanoma Research · doi:10.1097/cmr.0000000000000890 · Cited by 3 · see citing works
Nuclear expression of pSTAT3Tyr705 and pSTAT3Ser727 in the stromal compartment of localized hormone-naïve prostate cancer
Marginean, F. E., Hellsten, R., Krzyzanowska, A., & Bjartell, A. S. (2022) · Pathology - Research and Practice · doi:10.1016/j.prp.2022.153811 · Cited by 3 · see citing works

STAT3 activation
Rébé, C., Végran, F., Berger, H., & Ghiringhelli, F. (2013) · JAK-STAT · doi:10.4161/jkst.23010 · Cited by 216 · see citing works
Self-citation
Highlighted STAT3 as a potential drug target for cancer therapy
Lee, H., Jeong, A. J., & Ye, S. (2019) · BMB Reports · doi:10.5483/bmbrep.2019.52.7.152 · Cited by 294 · see citing works
The role of STAT3 in leading the crosstalk between human cancers and the immune system
Wang, Y., Shen, Y., Wang, S., Shen, Q., & Zhou, X. (2017) · Cancer Letters · doi:10.1016/j.canlet.2017.12.003 · Cited by 340 · see citing works
Targeting STAT3 in Cancer Immunotherapy
Zou, S., Tong, Q., Liu, B., Huang, W., Tian, Y., & Fu, X. (2020) · Molecular Cancer · doi:10.1186/s12943-020-01258-7 · Cited by 1,075 · see citing works
STAT3 Activity Promotes Programmed-Death Ligand 1 Expression and Suppresses Immune Responses in Breast Cancer
Zerdes, I., Wallerius, M., Sifakis, E. G., Wallmann, T., Betts, S., Bartish, M., Tsesmetzis, N., Tobin, N. P., Coucoravas, C., Bergh, J. C. S., et al. (2019) · Cancers · doi:10.3390/cancers11101479 · Cited by 97 · see citing works

Authors: Rébé, C., & Ghiringhelli, F.
Affiliations: Inserm (FR)
Corresponding author: Rébé, Cédric
Ghiringhelli, François
ORCID: Rébé, Cédric
Ghiringhelli, François
Venue: Cancers
Publisher: MDPI AG
Published: 2019-08-30
Volume: 11
Issue: 9
Pages: 1280
ISSN: 2072-6694 (ISSN-L)
DOI: 10.3390/cancers11091280
PMC: PMC6770459
OpenAlex: W2970221585
Cited by: 129
References: 203
Citations by year: 2026: 13 · 2025: 22 · 2024: 29 · 2023: 17 · 2022: 14 · 2021: 13 · 2020: 16 · 2019: 5
FWCI: 1.17
Type: journal article
Language: en
Open access: gold
dx.doi.org
Licence: cc-by
creativecommons.org/licenses/by/4.0/ (vor)
Locations: Cancers (publishedVersion, cc-by)
Europe PMC (PubMed Central) (publishedVersion, cc-by)
PubMed Central (publishedVersion, cc-by)
PubMed (publishedVersion)
DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders: Ligue Contre le Cancer (Equipe labélisée)
Topics: Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
Life Sciences › Immunology and Microbiology › Immunology › T-cell and B-cell Immunology
Keywords: STAT3, tumor immune microenvironment, antitumor immunity, transcription factors, immune cell activation, myeloid cells, lymphoid cells, STAT3 phosphorylation, STAT3 acetylation, immune checkpoint, tumor progression

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STAT3, a master regulator of anti-tumor immune response

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