ArticleFrontiers in immunology2023
Adrenergic receptor signaling regulates the CD40-receptor mediated anti-tumor immunity.
Article in Frontiers in immunology, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Neuro-immune interactions in tumors, immune-related disorders, and infections.Signal transduction and targeted therapy · 2026Review
- Neurotransmitters in cancer: how receptor signaling and posttranslational modifications modulate tumor progression and offer new therapeutic targets.Cell communication and signaling : CCS · 2026Review
- Role of the neurotransmitter-receptor pathway in T-cell tumor immunology and cancer immunotherapy.Acta biochimica et biophysica Sinica · 2026Review
- Identification and validation of cuproptosis-related immune checkpoint expression for glioblastoma.BMC cancer · 2025Article
- Neurotransmitters in tumors: chemical cross-talk shaping tumor progression.Biomarker research · 2025Review
- Sympathetic nervous system in tumor progression and metabolic regulation: mechanisms and clinical potential.Journal of translational medicine · 2025Review
- Chronic Psychological Stress in Oncogenesis: Multisystem Crosstalk and Multimodal Interventions.Research (Washington, D.C.) · 2025Review
- Neuroscience in peripheral cancers: tumors hijacking nerves and neuroimmune crosstalk.MedComm · 2024Review
- The Neuroimmune Axis and Its Therapeutic Potential for Primary Liver Cancer.International journal of molecular sciences · 2024Review
- The βFrontiers in immunology · 2024Article
- A Comprehensive Pan-cancer Analysis of the Biological Immunomodulatory Function and Clinical Value ofJournal of Cancer · 2024Article
- Advances on Delivery System of Active Ingredients of Dried Toad Skin and Toad Venom.International journal of nanomedicine · 2024Review
- Investigating the crosstalk between chronic stress and immune cells: implications for enhanced cancer therapy.Frontiers in neuroscience · 2023Review
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Authors and funding
2 authors.
Funding
Abstract
Inroduction: Anti-CD40 agonistic antibody (αCD40), an activator of dendritic cells (DC) can enhance antigen presentation and activate cytotoxic T-cells against poorly immunogenic tumors. However, cancer immunotherapy trials also suggest that αCD40 is only moderately effective in patients, falling short of achieving clinical success. Identifying factors that decrease αCD40 immune-stimulating effects can aid the translation of this agent to clinical reality. Method/Results: Here, we reveal that β-adrenergic signaling on DCs directly interferes with αCD40 efficacy in immunologically cold head and neck tumor model. We discovered that β-2 adrenergic receptor (β2AR) activation rewires CD40 signaling in DCs by directly inhibiting the phosphorylation of IκBα and indirectly by upregulating levels of phosphorylated-cAMP response element-binding protein (pCREB). Importantly, the addition of propranolol, a pan β-Blocker reprograms the CD40 pathways, inducing superior tumor regressions, increased infiltration of cytotoxic T-cells, and a reduced burden of regulatory T-cells in tumors compared to monotherapy. Discussion/Conclusion: Thus, our study highlights an important mechanistic link between stress-induced β2AR signaling and reduced αCD40 efficacy in cold tumors, providing a new combinatorial approach to improve clinical outcomes in patients.
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