The DOI matches its Crossref record; 27 of the 28 references it cites were found in a registry or an index.
Microbially Driven TLR5-Dependent Signaling Governs Distal Malignant Progression through Tumor-Promoting Inflammation
Open accessAbstract
The dominant TLR5(R392X) polymorphism abrogates flagellin responses in >7% of humans. We report that TLR5-dependent commensal bacteria drive malignant progression at extramucosal locations by increasing systemic IL-6, which drives mobilization of myeloid-derived suppressor cells (MDSCs). Mechanistically, expanded granulocytic MDSCs cause γδ lymphocytes in TLR5-responsive tumors to secrete galectin-1, dampening antitumor immunity and accelerating malignant progression. In contrast, IL-17 is consistently upregulated in TLR5-unresponsive tumor-bearing mice but only accelerates malignant progression in IL-6-unresponsive tumors. Importantly, depletion of commensal bacteria abrogates TLR5-dependent differences in tumor growth. Contrasting differences in inflammatory cytokines and malignant evolution are recapitulated in TLR5-responsive/unresponsive ovarian and breast cancer patients. Therefore, inflammation, antitumor immunity, and the clinical outcome of cancer patients are influenced by a common TLR5 polymorphism.
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“In contrast, the natural immunosurveillance of cancers can be negatively impacted by gut commensals through TLR5- and IL-6-dependent inflammation.”
From Melanoma and microbiota: Current understanding and future directions (2024) · cites this paper as [36]
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“The gut microbiome has been shown to have multiple effects on tumor biology, such as the transformation process, tumor progression, and the response to anticancer therapies including immunotherapy (21-29).”
From The human tumor microbiome is composed of tumor type–specific intracellular bacteria (2020) · cites this paper as [29]
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“The interaction resulted in IL-6-dependent mobilization of MDSCs and subsequently more γδT cells producing immunosuppressive galectin-1, followed by impaired antitumor response and accelerated malignant progression [60] (Fig. 2).”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [60]
In the citing paper
“The notion was further supported by another study showing bacterial flagellin stimulated pro-tumoral inflammation through TLR5 signaling [60].”
From Gut microbiota-mediated immunomodulation in tumor (2021) · cites this paper as [60]
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The human tumor microbiome is composed of tumor type–specific intracellular bacteria
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Metadata
- Authors
- Rutkowski, M. R., Stephen, T. L., Svoronos, N., Allegrezza, M. J., Tesone, A. J., Perales-Puchalt, A., Brencicova, E., Escovar-Fadul, X., Nguyen, J. M., Cadungog, M. G., Zhang, R., Salatino, M., Tchou, J., Rabinovich, G. A., & Conejo-Garcia, J. R.
- Affiliations
- The Wistar Institute (US)
- Christiana Care Health System (US)
- University of Pennsylvania (US)
- Abramson Cancer Center (US)
- Consejo Nacional de Investigaciones Científicas y Técnicas (AR)
- Corresponding author
- Conejo-Garcia, Jose R.
- ORCID
- Venue
- Cancer Cell
- Publisher
- Elsevier BV
- Published
- 2015-01
- Volume
- 27
- Issue
- 1
- Pages
- 27-40
- ISSN
- 1535-6108 (ISSN-L)
- PMC
- PMC4293269
- OpenAlex
- W2164918734
- Cited by
- 311
- References
- 28
- Citations by year
- 2026: 13 · 2025: 28 · 2024: 24 · 2023: 30 · 2022: 27 · 2021: 34 · 2020: 22 · 2019: 19 · 2018: 27 · 2017: 35 · 2016: 35 · 2015: 16
- FWCI
- 13.01
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cancer Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Conicet (submittedVersion, cc-by-nc-sa)
- Funders
- National Cancer Institute (CA010815, R01CA157664, U54CA151662, R01CA178687, R01CA163377, R01CA124515, T32CA009171, P30CA010815)
- Topics
- Life Sciences › Immunology and Microbiology › Immunology › Immune Response and Inflammation
- Life Sciences › Immunology and Microbiology › Immunology › Immune cells in cancer
- Life Sciences › Immunology and Microbiology › Immunology › Immunotherapy and Immune Responses
- Keywords
- TLR5, flagellin, commensal bacteria, tumor-promoting inflammation, myeloid-derived suppressor cells, granulocytic MDSCs, γδ T cells, galectin-1, interleukin-6, IL-17, antitumor immunity, malignant progression, ovarian cancer, breast cancer, microbiome
- MeSH terms
- Animals, Cells, Cultured, Humans, Mice, Inbred C57BL, Mice, Transgenic, Molecular Sequence Data, Neoplasm Transplantation, Neoplasms, Signal Transduction, Interleukin-6, Gene Expression Regulation, Neoplastic, Interleukin-17, Polymorphism, Single Nucleotide, Galectin 1, Cell Line, Tumor, Toll-Like Receptor 5, Mice, Microbiota
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