ArticleJournal of immunology (Baltimore, Md. : 1950)2015
TLR signaling modulates side effects of anticancer therapy in the small intestine.
Article in Journal of immunology (Baltimore, Md. : 1950), 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
58 citing papers in PubMed, 94 citations in OpenAlex.
- The gastrointestinal microbiome and constituent short-chain fatty acids: a narrative review of an underexplored axis in acute lymphoblastic leukemia.Gut pathogens · 2026Review
- Gut microbiome in advanced non-small cell lung cancer: effect of chemotherapy and impact on efficacy.Translational lung cancer research · 2026Article
- TLR2 activation potentiates P-glycoprotein-mediated methotrexate efflux and enhances cytotoxicity of human NK cells against acute lymphoblastic leukemia.Frontiers in immunology · 2026Article
- Increased expression of Toll-like receptors and associated alarmins in temporal arteries of patients with giant cell arteritis.Molecular medicine (Cambridge, Mass.) · 2025Article
- Bacterial Infections and Their Cell Wall Ligands Differentially Modulate Doxorubicin Sensitivity in Triple-Negative Breast Cancer Cells.Microorganisms · 2025Article
- Unraveling the complexity of radiotherapy- and chemotherapy-induced oral mucositis: insights into pathogenesis and intervention strategies.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2025Review
- Microbiome-mediated regulation of chemoradiotherapy response.Frontiers in oncology · 2025Review
- Crosstalk between gut microbiota and cancer chemotherapy: current status and trends.Discover oncology · 2024Article
- Updated perspectives on the contribution of the microbiome to the pathogenesis of mucositis using the MASCC/ISOO framework.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2024Review
- Influence of Gut Microbiota-Mediated Immune Regulation on Response to Chemotherapy.Pharmaceuticals (Basel, Switzerland) · 2024Review
- Role of the microbiota in response to and recovery from cancer therapy.Nature reviews. Immunology · 2024Review
- Low-Dose Chemotherapy Preferentially Shapes the Ileal Microbiome and Augments the Response to Immune Checkpoint Blockade by Activating AIM2 Inflammasome in Ileal Epithelial Cells.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Pharmacomicrobiomics of cell-cycle specific anti-cancer drugs - is it a new perspective for personalized treatment of cancer patients?Gut microbes · 2023Review
- Microbial sensing in the intestine.Protein & cell · 2023Review
- The Impact of Oral Antibiotics Prior to Cancer Diagnosis on Overall Patient Survival: Findings from an English Population-Based Cohort Study.Current oncology (Toronto, Ont.) · 2023Article
- Intratumoural microbiota: from theory to clinical application.Cell communication and signaling : CCS · 2023Review
- Experimental Chemotherapy-Induced Mucositis: A Scoping Review Guiding the Design of Suitable Preclinical Models.International journal of molecular sciences · 2022Article
- Clinical Significance of Lipid Transport Function of ABC Transporters in the Innate Immune System.Membranes · 2022Review
- Facts and Hopes for Gut Microbiota Interventions in Cancer Immunotherapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2022Review
- The science of mucositis.Supportive care in cancer : official journal of the Multinational Association of Supportive Care in Cancer · 2022Article
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 2 countries.
Funding
Abstract
Intestinal mucositis represents the most common complication of intensive chemotherapy, which has a severe adverse impact on quality of life of cancer patients. However, the precise pathophysiology remains to be clarified, and there is so far no successful therapeutic intervention. In this study, we investigated the role of innate immunity through TLR signaling in modulating genotoxic chemotherapy-induced small intestinal injury in vitro and in vivo. Genetic deletion of TLR2, but not MD-2, in mice resulted in severe chemotherapy-induced intestinal mucositis in the proximal jejunum with villous atrophy, accumulation of damaged DNA, CD11b(+)-myeloid cell infiltration, and significant gene alterations in xenobiotic metabolism, including a decrease in ABCB1/multidrug resistance (MDR)1 p-glycoprotein (p-gp) expression. Functionally, stimulation of TLR2 induced synthesis and drug efflux activity of ABCB1/MDR1 p-gp in murine and human CD11b(+)-myeloid cells, thus inhibiting chemotherapy-mediated cytotoxicity. Conversely, TLR2 activation failed to protect small intestinal tissues genetically deficient in MDR1A against DNA-damaging drug-induced apoptosis. Gut microbiota depletion by antibiotics led to increased susceptibility to chemotherapy-induced mucosal injury in wild-type mice, which was suppressed by administration of a TLR2 ligand, preserving ABCB1/MDR1 p-gp expression. Findings were confirmed in a preclinical model of human chemotherapy-induced intestinal mucositis using duodenal biopsies by demonstrating that TLR2 activation limited the toxic-inflammatory reaction and maintained assembly of the drug transporter p-gp. In conclusion, this study identifies a novel molecular link between innate immunity and xenobiotic metabolism. TLR2 acts as a central regulator of xenobiotic defense via the multidrug transporter ABCB1/MDR1 p-gp. Targeting TLR2 may represent a novel therapeutic approach in chemotherapy-induced intestinal mucositis.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.