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]
In the citing paper
“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]
In the citing paper
“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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Cites
A microbial symbiosis factor prevents intestinal inflammatory disease
Mazmanian, S. K., Round, J. L., & Kasper, D. L. (2008) · Nature · doi:10.1038/nature07008 · Cited by 2,340
Commensal Bacteria Control Cancer Response to Therapy by Modulating the Tumor Microenvironment
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IL-17 can promote tumor growth through an IL-6–Stat3 signaling pathway
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Items 301–311 of 311
Multidisciplinary Approaches in Head and Neck Cancer
Chipiti, T., Luvhengo, T. E., Mabvakure, B. M., & Dlamini, Z. (2025) · doi:10.1093/med/9780197794197.003.0009
El-Sayed, S. M., Mohamed, M. R., Naguib, M. M., Aglan, H. A., & Ahmed, H. H. (2025) · Inflammopharmacology · doi:10.1007/s10787-025-02078-1 · Cited by 1
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Correlation of Galectin Family Expression with Glioblastoma Progression and Survival
Curpen, P., Ahmady, F., Carnie, B. M. H., Anderson, G. E. C., Kannourakis, G., Sharma, A., Achuthan, A. A., & Luwor, R. B. (2025) · International Journal of Molecular Sciences · doi:10.3390/ijms27010417
A Developmental Lectin-Glycan Program Enables Early Breast Cancer Dissemination and Metastatic OnsetPreprint
Perrotta, R. M., Bertón, M., Salazar, L. E. V., Mahmoud, Y. D., Sáez, J. M. P., Dalotto‐Moreno, T., del Valle‐Pérez, B., Martínez‐Bosch, N., Morales, R. M., Gatto, S. G., et al. (2026) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.64898/2026.02.23.707584
Self-citationLung microbiota analysis in early-stage lung adenocarcinoma
Sun, K., Li, B., Zhang, C., Zhou, K., Zheng, Z., Gao, C., Lin, Y., Zhang, N., Wang, Z., Li, J., et al. (2026) · Microbiology Spectrum · doi:10.1128/spectrum.01987-25
Immunomodulation des lymphocytes Vγ9Vδ2 dans les leucémies aigües
Floch, A.-C. L. (2023) · theses.fr (ABES) · doi:10.70675/b4e332efz0a66z4c9az85eaz8eea012e9839
Microbiome—pancreatic cancer crosstalk: From tumor biology to therapeutic intervention
薛玉芹, Ye, J., Wang, S., Liu, M., Dai, F., Bai, M., Wang, Y., Savoji, A., Wang, Y., Hylemon, P. B., et al. (2026) · iMetaOmics. · doi:10.1002/imo2.70126
Intratumoral Microbiome–Tumor Microenvironment Crosstalk in Breast Cancer Aggressiveness
Mushii, O., Lukianova, Y., & Bazas, V. (2026) · The Breast Journal · doi:10.1155/tbj/1508684
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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