Hyperactivation of STAT3 is involved in abnormal differentiation of dendritic cells in cancer
Open accessAbstract
Abnormal differentiation of myeloid cells is one of the hallmarks of cancer. However, the molecular mechanisms of this process remain elusive. In this study, we investigated the effect of tumor-derived factors on Janus kinase (Jak)/STAT signaling in myeloid cells during their differentiation into dendritic cells. Tumor cell conditioned medium induced activation of Jak2 and STAT3, which was associated with an accumulation of immature myeloid cells. Jak2/STAT3 activity was localized primarily in these myeloid cells, which prevented the differentiation of immature myeloid cells into mature dendritic cells. This differentiation was restored after removal of tumor-derived factors. Inhibition of STAT3 abrogated the negative effects of these factors on myeloid cell differentiation, and overexpression of STAT3 reproduced the effects of tumor-derived factors. Thus, this is a first demonstration that tumor-derived factors may affect myeloid cell differentiation in cancer via constitutive activation of Jak2/STAT3.
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Inhibition of JAK/STAT3 signaling improves mature dendritic cell function and augments antitumor immunity.
“inhibition of JAK/STAT3 signaling improves mature DC function and augments antitumor immunity”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Nefedova et al., 2004
In “Increased STAT3 activity is directly involved in accumulation of ImCs and decreased DC differentiation,” blocking STAT3 in progenitor cells restored their differentiation into mature DCs. The “Discussion” proposes that STAT3 inhibition may improve immune responses in cancer, but does not demonstrate augmented antitumor immunity. It also reports that reducing STAT3 activity in activated DCs did not improve their function, so the claim about improved mature DC function is not supported. (LLM, conf=0.90)
Experimental — accuracy not yet measuredIL-6- and IL-10-stimulated STAT3 suppresses dendritic cell maturation and activation and promotes immune tolerance.
“IL-6– and IL-10–stimulated STAT3 is also known to suppress DC maturation and activation and promote immune tolerance”
From Targeting Janus Kinases and Signal Transducer and Activator of Transcription 3 To Treat Inflammation, Fibrosis, and Cancer: Rationale, Progress, and Caution (2020) · cites this paper as Nefedova et al., 2004
The sections on STAT3 activity in DCs and decreased DC differentiation report that tumor-derived factors maintain STAT3 activity, impair DC maturation and reduce their ability to stimulate T cells. The paper identifies IL-10 as a STAT3 activator and finds that blocking it has a modest effect on tumor-conditioned STAT3 activity, but it does not establish the claimed IL-6– and IL-10–stimulated mechanism or show that it promotes immune tolerance. Page numbers are unavailable in our copy. (LLM, conf=0.86)
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Cites
Imada, K., & Leonard, W. J. (2000) · Molecular Immunology · doi:10.1016/s0161-5890(00)00018-3 · Cited by 610 · see citing works
Menetrier-Caux, C., Montmain, G., Dieu, M. C., Bain, C., Favrot, M. C., Caux, C., & Blay, J. Y. (1998) · Blood · doi:10.1182/blood.v92.12.4778 · Cited by 590 · see citing works
Stat3-mediated Myc expression is required for Src transformation and PDGF-induced mitogenesis
Bowman, T., Broome, M. A., Sinibaldi, D., Wharton, W., Pledger, W. J., Sedivy, J. M., Irby, R., Yeatman, T., Courtneidge, S. A., & Jove, R. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.131568898 · Cited by 488 · see citing works
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Research works printed but not linked: 1
- Takeda, K., K. Noguchi, W. Shi, T. Tanaka, M. Matsumoto, N. Yoshida, T. Kishimoto, and S. Akira. 1997. Targeted disruption of the mouse Stat3 gene leads to early embryonic lethality. Proc. Natl. Acad. Sci. USA 94:3801.
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Bronte, V., Brandau, S., Chen, S.-H., Colombo, M. P., Frey, A. B., Greten, T. F., Mandruzzato, S., Murray, P. J., Ochoa, A., Ostrand-Rosenberg, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms12150 · Cited by 2,751 · see citing works
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Kumar, V., Patel, S., Tcyganov, E., & Gabrilovich, D. I. (2016) · Trends in Immunology · doi:10.1016/j.it.2016.01.004 · Cited by 2,008 · see citing works
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Vinay, D. S., Ryan, E. P., Pawelec, G., Talib, W. H., Stagg, J., Elkord, E., Lichtor, T., Decker, W. K., Whelan, R. L., Kumara, H. M. C. S., et al. (2015) · Seminars in Cancer Biology · doi:10.1016/j.semcancer.2015.03.004 · Cited by 1,625 · see citing works
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Araki, K., Turner, A. P., Shaffer, V. O., Gangappa, S., Keller, S. A., Bachmann, M. F., Larsen, C. P., & Ahmed, R. (2009) · Nature · doi:10.1038/nature08155 · Cited by 1,575 · see citing works
Corzo, C. A., Condamine, T., Lu, L., Cotter, M. J., Youn, J.-I., Cheng, P., Cho, H.-I., Celis, E., Quiceno, D. G., Padhya, T., et al. (2010) · Journal of Experimental Medicine · doi:10.1084/jem.20100587 · Cited by 1,173 · see citing works
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Combination strategies to maximize the benefits of cancer immunotherapy
Zhu, S., Zhang, T., Zheng, L., Liu, H., Song, W., Liu, D., Li, Z., & Pan, C.-X. (2021) · Journal of Hematology & Oncology · doi:10.1186/s13045-021-01164-5 · Cited by 654 · see citing works
Ostrand-Rosenberg, S., & Fenselau, C. (2018) · The Journal of Immunology · doi:10.4049/jimmunol.1701019 · Cited by 509 · see citing works
Kodumudi, K. N., Woan, K., Gilvary, D. L., Sahakian, E., Wei, S., & Djeu, J. Y. (2010) · Clinical Cancer Research · doi:10.1158/1078-0432.ccr-10-0733 · Cited by 500 · see citing works
Kumar, V., Cheng, P., Condamine, T., Mony, S., Languino, L. R., McCaffrey, J. C., Hockstein, N., Guarino, M., Masters, G., Penman, E., et al. (2016) · Immunity · doi:10.1016/j.immuni.2016.01.014 · Cited by 371 · see citing works
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Sica, A., & Massarotti, M. (2017) · Journal of Autoimmunity · doi:10.1016/j.jaut.2017.07.010 · Cited by 201 · see citing works
STAT3, a master regulator of anti-tumor immune response
Rébé, C., & Ghiringhelli, F. (2019) · Cancers · doi:10.3390/cancers11091280 · Cited by 129 · see citing works
Ray, A., Chakraborty, K., & Ray, P. (2013) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2013.00052 · Cited by 108 · see citing works
Tumor microenvironment-related dendritic cell deficiency: a target to enhance tumor immunotherapy
Zhu, S., Yang, N., Wu, J., Wang, X., Wang, W., Liu, Y.-J., & Chen, J. (2020) · Pharmacological Research · doi:10.1016/j.phrs.2020.104980 · Cited by 71 · see citing works
Biological Hallmarks and Emerging Strategies to Target STAT3 Signaling in Multiple Myeloma
Zhou, J., & Chng, W.-J. (2022) · Cells · doi:10.3390/cells11060941 · Cited by 22 · see citing works
- Authors
- Nefedova, Y., Huang, M., Kusmartsev, S., Bhattacharya, R., Cheng, P., Salup, R., Jove, R., & Gabrilovich, D.
- Affiliations
- University of South Florida (US)
- Venue
- The Journal of Immunology
- Publisher
- Oxford University Press (OUP)
- Published
- 2004-01-01
- Volume
- 172
- Issue
- 1
- Pages
- 464-474
- ISSN
- 0022-1767 (ISSN-L)
- 1550-6606
- OpenAlex
- W1960585934
- Cited by
- 464
- References
- 3
- Citations by year
- 2026: 6 · 2025: 11 · 2024: 14 · 2023: 27 · 2022: 20 · 2021: 26 · 2020: 19 · 2019: 19 · 2018: 16 · 2017: 20 · 2016: 32 · 2015: 23 · 2014: 24 · 2013: 33 · 2012: 23
- FWCI
- 11.55
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Immunology (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Oncology › Cytokine Signaling Pathways and Interactions
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- JAK2/STAT3 signaling, dendritic cell differentiation, myeloid differentiation, tumor-derived factors, immature myeloid cells, STAT3 inhibition
- MeSH terms
- Animals, Cell Aggregation, Cell Differentiation, Cell Division, Colonic Neoplasms, Dendritic Cells, DNA-Binding Proteins, Female, Growth Inhibitors, Hematopoietic Stem Cells, Mice, Inbred BALB C, Mice, Inbred C57BL, Neoplasm Proteins, Protein-Tyrosine Kinases, Proto-Oncogene Proteins, Signal Transduction, Trans-Activators, Up-Regulation, Myeloid Cells, NIH 3T3 Cells, Cell Line, Tumor, STAT3 Transcription Factor, Mice, Janus Kinase 2
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