ArticleProceedings of the National Academy of Sciences of the United States of America2020
Sufficiency of CD40 activation and immune checkpoint blockade for T cell priming and tumor immunity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 105 papers, 1 of them a synthesis that pooled it.
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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
105 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Improving Outcomes in Pancreatic Adenocarcinoma: A Systematic Review of Immunotherapy in Multimodal Treatment.Medicina (Kaunas, Lithuania) · 2025Pooled it
- Intratumoral Sotigalimab with Pembrolizumab Induces Rapid Activation of Antigen-Presenting Cells and Drives Antitumor Responses in Non-injected Tumors in Metastatic Melanoma: A Phase I/II Study.Cancer discovery · 2026Trial
- A Phase II Trial of the CD40 Agonistic Antibody Sotigalimab (APX005M) in Combination with Nivolumab in Subjects with Metastatic Melanoma with Confirmed Disease Progression on Anti-PD-1 Therapy.Clinical cancer research : an official journal of the American Association for Cancer Research · 2024Trial
- Systemic inflammation is a determinant of outcomes of CD40 agonist-based therapy in pancreatic cancer patients.JCI insight · 2021Trial
- Decoding spatiotemporal fibrotic and cellular immunosuppression of therapeutic T cells in live pancreatic ductal adenocarcinoma.Molecular systems biology · 2026Article
- IFNγ-dependent tumor-cell MHC-II is restrained by MAPK signaling and associated with immunotherapy responsiveness in pancreatic ductal adenocarcinoma.Cancer immunology research · 2026Article
- Review
- Focused ultrasound thermal ablation and CD40 agonism reprograms breast tumor immunity to drive regression and memory.Journal for immunotherapy of cancer · 2026Article
- Dendritic cell redundancy enables priming of anti-tumor CD4Cancer cell · 2026Article
- CD40 Agonist Therapy in Melanoma: Translating Preclinical Promise Into Clinical Practice.Pigment cell & melanoma research · 2026Review
- CD40 Agonism in Pancreatic Ductal Adenocarcinoma: Expression, Biology, and Therapeutic Targeting.Cancers · 2026Review
- Article
- Systolic pressure overload caused pulmonary oxidative stress, vessel remodeling and severe microvascular thrombosis in CD40 knockout mice through promoting platelet aggregation.Redox biology · 2026Article
- Article
- A CD40-OX40 co-stimulatory circuit orchestrates protective CD4Molecular therapy : the journal of the American Society of Gene Therapy · 2026Article
- Engineering lipid nanoparticle-stabilized emulsions for spatiotemporal mRNA delivery and enhanced T cell immunity.Cell reports. Medicine · 2026Article
- Focused Ultrasound Thermal Ablation and CD40 Agonism Reprograms Breast Tumor Immunity to Drive Regression and Memory.bioRxiv : the preprint server for biology · 2026Article
- Agonistic CD40 elicits CD8+ T-cell-dependent primary responses and CD4+ T-cell-dependent long-term immunity in breast cancer.NPJ breast cancer · 2026Article
- Positioning and reversible suppression of CCR7Immunity · 2026Article
- CD4+ T Cells Mediate MHC-Deficient Tumor Rejection and Endothelial Cell Reprogramming.Cancer immunology research · 2026Article
45 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Innate immune receptors such as toll-like receptors (TLRs) provide critical molecular links between innate cells and adaptive immune responses. Here, we studied the CD40 pathway as an alternative bridge between dendritic cells (DCs) and adaptive immunity in cancer. Using an experimental design free of chemo- or radiotherapy, we found CD40 activation with agonistic antibodies (⍺CD40) produced complete tumor regressions in a therapy-resistant pancreas cancer model, but only when combined with immune checkpoint blockade (ICB). This effect, unachievable with ICB alone, was independent of TLR, STING, or IFNAR pathways. Mechanistically, αCD40/ICB primed durable T cell responses, and efficacy required DCs and host expression of CD40. Moreover, ICB drove optimal generation of polyfunctional T cells in this "cold" tumor model, instead of rescuing T cell exhaustion. Thus, immunostimulation via αCD40 is sufficient to synergize with ICB for priming. Clinically, combination αCD40/ICB may extend efficacy in patients with "cold" and checkpoint-refractory tumors.
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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.