ArticleCancer immunology research2015
Systemic Agonistic Anti-CD40 Treatment of Tumor-Bearing Mice Modulates Hepatic Myeloid-Suppressive Cells and Causes Immune-Mediated Liver Damage.
Article in Cancer immunology research, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
43 citing papers in PubMed, 56 citations in OpenAlex.
- Focused ultrasound thermal ablation and CD40 agonism reprograms breast tumor immunity to drive regression and memory.Journal for immunotherapy of cancer · 2026Article
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Article
- IL1R1 blockade augments CD40 agonist mediated immunity in pancreatic cancer.Scientific reports · 2026Article
- Focused Ultrasound Thermal Ablation and CD40 Agonism Reprograms Breast Tumor Immunity to Drive Regression and Memory.bioRxiv : the preprint server for biology · 2026Article
- A low-dose immunotherapy targeting Fc gamma Receptors and heparan sulfate proteoglycan to impact myeloid cells and control cancers with diverse immunosuppressive profiles.Frontiers in immunology · 2026Article
- MDSCs in Breast Cancer: Metastasis, Lipid Metabolism, and Therapeutics.Molecular cancer research : MCR · 2025Review
- Immune microenvironment in hepatocellular carcinoma: from pathogenesis to immunotherapy.Cellular & molecular immunology · 2025Review
- Ponatinib Averts αCD40 Antibody Mediated Toxicity by Lowering MAPK38 Expression and Shows Proimmunogenic Effects in a Murine Tumor Model.ACS pharmacology & translational science · 2025Article
- CD8Science advances · 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
- Sequential STING and CD40 agonism drives massive expansion of tumor-specific T cells in liposomal peptide vaccines.Cellular & molecular immunology · 2025Article
- Genetically engineered IgG1 and nanobody oligomers acquire strong intrinsic CD40 agonism.Bioengineered · 2024Article
- Fcγ-Receptor-Independent Controlled Activation of CD40 Canonical Signaling by Novel Therapeutic Antibodies for Cancer Therapy.Antibodies (Basel, Switzerland) · 2024Article
- Harnessing the potential of CD40 agonism in cancer therapy.Cytokine & growth factor reviews · 2024Review
- Genomic and Transcriptomic Landscape of an Oral Squamous Cell Carcinoma Mouse Model for Immunotherapy.Cancer immunology research · 2023Article
- Kupffer cells prevent pancreatic ductal adenocarcinoma metastasis to the liver in mice.Nature communications · 2023Article
- Sustained Intratumoral Administration of Agonist CD40 Antibody Overcomes Immunosuppressive Tumor Microenvironment in Pancreatic Cancer.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- Immunotoxin-αCD40 therapy activates innate and adaptive immunity and generates a durable antitumor response in glioblastoma models.Science translational medicine · 2023Article
- FcγRs and Their Relevance for the Activity of Anti-CD40 Antibodies.International journal of molecular sciences · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
Immune-stimulatory mAbs are currently being evaluated as antitumor agents. Although overall toxicity from these agents appears to be moderate, liver toxicities have been reported and are not completely understood. We studied the effect of systemic CD40 antibody treatment on myeloid cells in the spleen and liver. Naïve and tumor-bearing mice were treated systemically with agonistic anti-CD40 antibody. Immune cell subsets in the liver and spleen, serum transaminases, and liver histologies were analyzed after antibody administration. Nox2(-/-), Cd40(-/-), and bone marrow chimeric mice were used to study the mechanism by which agonistic anti-CD40 mediates its effects in vivo. Suppressor function of murine and human tumor-induced myeloid-derived suppressor cells (MDSC) was studied upon CD40 ligation. Agonistic CD40 antibody caused liver damage within 24 hours after injection in two unrelated tumor models and mice strains. Using bone marrow chimeras, we demonstrate that CD40 antibody-induced hepatitis in tumor-bearing mice was dependent on the presence of CD40-expressing hematopoietic cells. Agonistic CD40 ligation-dependent liver damage was induced by the generation of reactive oxygen species. Furthermore, agonistic CD40 antibody resulted in increased CD80-positive and CD40-positive liver CD11b(+)Gr-1(+) immature myeloid cells. CD40 ligation on tumor-induced murine and human CD14(+)HLA-DR(low) peripheral blood mononuclear cells from patients with cancer reduced their immune suppressor function. Collectively, agonistic CD40 antibody treatment activated tumor-induced myeloid cells, caused myeloid-dependent hepatotoxicity, and ameliorated the suppressor function of murine and human MDSC. Collectively, our data suggest that CD40 may mature immunosuppressive myeloid cells and thereby cause liver damage in mice with an accumulation of tumor-induced hepatic MDSC.
Indexed as
Identifiers
What OpenQuestion holds
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.