ArticleJournal for immunotherapy of cancer2024
TNFR2 blockade promotes antitumoral immune response in PDAC by targeting activated Treg and reducing T cell exhaustion.
Article in Journal for immunotherapy of cancer, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed.
- Single-cell RNA sequencing uncovers an immunosuppressive program in PDAC mast cells: tumour-driven activation, proliferation, and association with Treg recruitment.Annals of medicine · 2026Article
- Mapping the TNFR2-targeting antibody patent landscape: Insights from macro trends to structural signatures.Human vaccines & immunotherapeutics · 2026Article
- The multifaceted landscape of T cell exhaustion in organ transplantation: From molecular mechanisms (epigenetics, transcription, metabolism) to induction strategies.Genes & diseases · 2026Review
- Combination of APS, HMGN1, and anti-TNFR2 antibody remodels the tumor immune microenvironment to enhance antitumor immunity in colorectal cancer.Translational oncology · 2026Article
- T Cell Exhaustion in Cancer Immunotherapy: Heterogeneity, Mechanisms, and Therapeutic Opportunities.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Review
- Informed spatially aware patterns for multiplexed immunofluorescence data.Scientific reports · 2026Article
- Emerging Chimeric Antigen Receptor-Immune Cell Therapy for Pancreatic Cancer: Mechanisms, Clinical Advances, and Future Perspectives.Oncology research · 2026Review
- Regulatory T cells in breast cancer drivers of immune suppression and targets for immunotherapy.Frontiers in immunology · 2026Review
- Antibody targeting of the TNF-TNFR2 axis to overcome tumor immune resistance.Frontiers in immunology · 2026Review
- Remodeling the Tumor Microenvironment: Mechanistic Insights and Translational Frontiers of TCM-Derived Bioactive Monomers.Cancer management and research · 2026Review
- A bispecific antibody targeting PD-L1/TNFR2 increases tumor targeting and enhances antitumor efficacy in colorectal cancer.Journal for immunotherapy of cancer · 2025Article
- TNF Production or TNFR2 Expression Characterize Distinct States of Regulatory T Cells that Cooperate in Treg Expansion in Cancer and Chronic Inflammation.European journal of immunology · 2025Article
- Review
- Metabolic, transcriptomic, and proteomic adaptations in pancreatic ductal adenocarcinoma-patient derived xenograft models across serial passages.Journal of translational medicine · 2025Article
- Machine Learning-Based WGCNA Approach for Developing an Immunogenic Cell Death-Related Hub Gene Signature and Identification of AJM1 as a Prognostic Biomarker in Pancreatic Adenocarcinoma.International journal of medical sciences · 2025Article
- Novel nanobody-161 binds tumor necrosis factor receptor 2 (TNFR2) to exert an anti-tumor effect but does not block TNFα-binding.Frontiers in immunology · 2025Article
- Epigenetic regulation of CD8Frontiers in immunology · 2025Review
- Immunosuppressive tumor microenvironment in pancreatic cancer: mechanisms and therapeutic targets.Frontiers in immunology · 2025Review
Corrections and comments
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Authors and funding
18 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundPancreatic ductal adenocarcinoma (PDAC) is one of the most aggressive cancers, highly resistant to standard chemotherapy and immunotherapy. Regulatory T cells (Tregs) expressing tumor necrosis factor α receptor 2 (TNFR2) contribute to immunosuppression in PDAC. Treg infiltration correlates with poor survival and tumor progression in patients with PDAC. We hypothesized that TNFR2 inhibition using a blocking monoclonal antibody (mAb) could shift the Treg-effector T cell balance in PDAC, thus enhancing antitumoral responses.
methodTo support this hypothesis, we first described TNFR2 expression in a cohort of 24 patients with PDAC from publicly available single-cell analysis data. In orthotopic and immunocompetent mouse models of PDAC, we also described the immune environment of PDAC after immune cell sorting and single-cell analysis. The modifications of the immune environment before and after anti-TNFR2 mAb treatment were evaluated as well as the effect on tumor progression.
resultsPatients with PDAC exhibited elevated TNFR2 expression in Treg, myeloid cells and endothelial cells and lower level in tumor cells. By flow cytometry and single-cell RNA-seq analysis, we identified two Treg populations in orthotopic mouse models: Resting and activated Tregs. The anti-TNFR2 mAb selectively targeted activated tumor-infiltrating Tregs, reducing T cell exhaustion markers in CD8
conclusionOur data suggest that combining a CD40 agonist with a TNFR2 antagonist represents a promising therapeutic strategy for patients with PDAC.
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