ArticleCell reports. Medicine2021
The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.
Article in Cell reports. Medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed.
- The gut-liver axis in drug-induced liver injury (DILI): Interplay between gut microbiota, intestinal barrier, and immune system.Acta pharmaceutica Sinica. B · 2026Review
- Vonoprazan is associated with a phenotype-specific increase in cholangitis reporting in immune checkpoint inhibitor-treated patients: a VigiBase pharmacovigilance study.Journal of gastroenterology · 2026Article
- Bortezomib-induced gastrointestinal dysfunction, peripheral neuropathy and neuroimmune signalling are influenced by the gut microbiota in mice.Journal of neuroinflammation · 2026Article
- Selective elimination of circulating effector CD8 T cells via LTβR blockade separates anti-CD137 efficacy from toxicity.Science advances · 2026Article
- IL1R1 blockade augments CD40 agonist mediated immunity in pancreatic cancer.Scientific reports · 2026Article
- The impact of concomitant medications on treatment outcomes in patients with cancer receiving immune checkpoint inhibitors.Nature reviews. Cancer · 2026Review
- Metabolism-Driven Modulation by the Human Microbiota: Implications for Cancer Therapy and Emerging Strategies.Advances in experimental medicine and biology · 2026Review
- Intratumoral delivery of FLT3L with CXCR3/CCR5 ligands promotes XCR1Nature communications · 2025Article
- Gut microbiota shapes cancer immunotherapy responses.NPJ biofilms and microbiomes · 2025Review
- Exploring the Causal Association Between 91 Circulating Inflammatory Proteins and Neurodegenerative Diseases: A Bidirectional Two-Sample Mendelian Randomization and Bioinformatics Analysis.Brain and behavior · 2025Article
- Identification and impact of microbiota-derived metabolites in ascites of ovarian and gastrointestinal cancer.Cancer & metabolism · 2025Article
- Single-cell transcriptomic analysis reveals gut microbiota-immunotherapy synergy through modulating tumor microenvironment.Signal transduction and targeted therapy · 2025Article
- IL-1R1 Blockade Boosts CD40 Agonist Immune Responses but Fails to Improve Efficacy or Reduce Hepatotoxicity in Pancreatic Cancer.bioRxiv : the preprint server for biology · 2025Article
- Insights into the gut-liver axis: mechanisms and emerging therapies in hepatocellular carcinoma.Frontiers in pharmacology · 2025Review
- Article
- Microbial metabolites and their influence on the tumor microenvironment.Frontiers in immunology · 2025Review
- Role of the microbiota in response to and recovery from cancer therapy.Nature reviews. Immunology · 2024Review
- Evaluation of a Combinatorial Immunotherapy Regimen That Can Cure Mice Bearing MYCN-Driven High-Risk Neuroblastoma That Resists Current Clinical Therapy.Journal of clinical medicine · 2024Article
- An Analysis of the Gut Microbiota and Related Metabolites following PCSK9 Inhibition in Statin-Treated Patients with Elevated Levels of Lipoprotein(a).Microorganisms · 2024Article
- What we need to know about the germ-free animal models.AIMS microbiology · 2024Review
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18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immune agonist antibodies (IAAs) are promising immunotherapies that target co-stimulatory receptors to induce potent anti-tumor immune responses, particularly when combined with checkpoint inhibitors. Unfortunately, their clinical translation is hampered by serious dose-limiting, immune-mediated toxicities, including high-grade and sometimes fatal liver damage, cytokine release syndrome (CRS), and colitis. We show that the immunotoxicity, induced by the IAAs anti-CD40 and anti-CD137, is dependent on the gut microbiota. Germ-free or antibiotic-treated mice have significantly reduced colitis, CRS, and liver damage following IAA treatment compared with conventional mice or germ-free mice recolonized via fecal microbiota transplant. MyD88 signaling is required for IAA-induced CRS and for anti-CD137-induced, but not anti-CD40-induced, liver damage. Importantly, antibiotic treatment does not impair IAA anti-tumor efficacy, alone or in combination with anti-PD1. Our results suggest that microbiota-targeted therapies could overcome the toxicity induced by IAAs without impairing their anti-tumor activity.
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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.