ArticleJournal of immunology (Baltimore, Md. : 1950)2016
CSF-1R-Dependent Lethal Hepatotoxicity When Agonistic CD40 Antibody Is Given before but Not after Chemotherapy.
Article in Journal of immunology (Baltimore, Md. : 1950), 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 43 papers, 1 of them a synthesis that pooled it.
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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
43 citing papers in PubMed, 1 synthesis or guideline pooled it, 61 citations in OpenAlex.
- Global assessment of hepatic safety in novel immunotherapies: a systematic review and meta-analysis.Frontiers in immunology · 2025Pooled it
- Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients.JCI insight · 2021Trial
- Macrophage Plasticity in Cancer Therapy: Function, Timing, and Tradeoffs.International journal of molecular sciences · 2026Review
- Tumor-associated macrophages in the tumor immune microenvironment of non-small cell lung cancer.Frontiers in immunology · 2026Review
- 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
- Single Treatment Boiling Histotripsy Focused Ultrasound Ablation Neither Negates nor Enhances the Activity of α-CD40 in a Pancreatic Cancer Model.IEEE transactions on bio-medical engineering · 2025Article
- 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
- Fcγ-Receptor-Independent Controlled Activation of CD40 Canonical Signaling by Novel Therapeutic Antibodies for Cancer Therapy.Antibodies (Basel, Switzerland) · 2024Article
- Stocking the toolbox-Using preclinical models to understand the development and treatment of immune checkpoint inhibitor-induced immune-related adverse events.Immunological reviews · 2023Review
- Signaling pathways involved in the biological functions of dendritic cells and their implications for disease treatment.Molecular biomedicine · 2023Review
- Antibody-induced erythrophagocyte reprogramming of Kupffer cells prevents anti-CD40 cancer immunotherapy-associated liver toxicity.Journal for immunotherapy of cancer · 2023Article
- Injectable Nanoparticle-Based Hydrogels Enable the Safe and Effective Deployment of Immunostimulatory CD40 Agonist Antibodies.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Article
- Avidity in antibody effector functions and biotherapeutic drug design.Nature reviews. Drug discovery · 2022Review
- CD40 stimulation as a molecular adjuvant for cancer vaccines and other immunotherapies.Cellular & molecular immunology · 2022Review
- Macrophage-Based Combination Therapies as a New Strategy for Cancer Immunotherapy.Kidney diseases (Basel, Switzerland) · 2022Review
- The immunotoxicity, but not anti-tumor efficacy, of anti-CD40 and anti-CD137 immunotherapies is dependent on the gut microbiota.Cell reports. Medicine · 2021Article
- TNF blockade uncouples toxicity from antitumor efficacy induced with CD40 chemoimmunotherapy.JCI insight · 2021Article
- Resident Kupffer cells and neutrophils drive liver toxicity in cancer immunotherapy.Science immunology · 2021Article
- cIAP1/2 antagonism eliminates MHC class I-negative tumors through T cell-dependent reprogramming of mononuclear phagocytes.Science translational medicine · 2021Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
Cancer immunotherapies are increasingly effective in the clinic, especially immune checkpoint blockade delivered to patients who have T cell-infiltrated tumors. Agonistic CD40 mAb promotes stromal degradation and, in combination with chemotherapy, drives T cell infiltration and de novo responses against tumors, rendering resistant tumors susceptible to current immunotherapies. Partnering anti-CD40 with different treatments is an attractive approach for the next phase of cancer immunotherapies, with a number of clinical trials using anti-CD40 combinations ongoing, but the optimal therapeutic regimens with anti-CD40 are not well understood. Pancreatic ductal adenocarcinoma (PDA) is classically resistant to immunotherapy and lacks baseline T cell infiltration. In this study, we used a tumor cell line derived from a genetically engineered mouse model of PDA to investigate alterations in the sequence of anti-CD40 and chemotherapy as an approach to enhance pharmacological delivery of chemotherapy. Unexpectedly, despite our previous studies showing anti-CD40 treatment after chemotherapy is safe in both mice and patients with PDA, we report in this article that anti-CD40 administration <3 d in advance of chemotherapy is lethal in more than half of treated C57BL/6 mice. Anti-CD40 treatment 2 or 3 d before chemotherapy resulted in significantly increased populations of both activated myeloid cells and macrophages and lethal hepatotoxicity. Liver damage was fully abrogated when macrophage activation was blocked using anti-CSF-1R mAb. These studies highlight the dual nature of CD40 in activating both macrophages and T cell responses, and the need for preclinical investigation of optimal anti-CD40 treatment regimens for safe design of clinical trials.
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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.