ArticleOncotarget2016
Phenotypic screening reveals TNFR2 as a promising target for cancer immunotherapy.
Article in Oncotarget, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 36 papers.
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Who cites it
36 citing papers in PubMed, 54 citations in OpenAlex.
- Tumor-Infiltrating mregDCs Restrain Anti-Tumor Immunity in Early Relapse HCC.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Decoding TNF receptor superfamily control of CD4Cell communication and signaling : CCS · 2026Review
- 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
- Lactylation-driven TNFR2 expression in regulatory T cells promotes the progression of malignant pleural effusion.Journal for immunotherapy of cancer · 2024Article
- Targeting TNFR2 for cancer immunotherapy: recent advances and future directions.Journal of translational medicine · 2024Review
- Article
- Soluble receptors in cancer: mechanisms, clinical significance, and therapeutic strategies.Experimental & molecular medicine · 2024Review
- Sequence enrichment profiles enable target-agnostic antibody generation for a broad range of antigens.Cell reports methods · 2023Article
- The Immunosuppressive Effect of TNFR2 Expression in the Colorectal Cancer Microenvironment.Biomedicines · 2023Review
- Deep Mining of Complex Antibody Phage Pools.Methods in molecular biology (Clifton, N.J.) · 2023Article
- Therapeutic potential of TNFR2 agonists: a mechanistic perspective.Frontiers in immunology · 2023Review
- TNFR2 antagonist and agonist: a potential therapeutics in cancer immunotherapy.Medical oncology (Northwood, London, England) · 2022Review
- Protein scaffolds: antibody alternatives for cancer diagnosis and therapy.RSC chemical biology · 2022Review
- Review
- The effects of TNF-α/TNFR2 in regulatory T cells on the microenvironment and progression of gastric cancer.International journal of cancer · 2022Article
- Combination cancer immunotherapy targeting TNFR2 and PD-1/PD-L1 signaling reduces immunosuppressive effects in the microenvironment of pancreatic tumors.Journal for immunotherapy of cancer · 2022Article
- Targeting TNFR2: A Novel Breakthrough in the Treatment of Cancer.Frontiers in oncology · 2022Review
- A TNFR2 antibody by countering immunosuppression cooperates with HMGN1 and R848 immune stimulants to inhibit murine colon cancer.International immunopharmacology · 2021Article
- TNFα and Immune Checkpoint Inhibition: Friend or Foe for Lung Cancer?International journal of molecular sciences · 2021Review
- Chemotherapy Shifts the Balance in Favor of CD8+ TNFR2+ TILs in Triple-Negative Breast Tumors.Cells · 2021Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
23 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Antibodies that target cell-surface molecules on T cells can enhance anti-tumor immune responses, resulting in sustained immune-mediated control of cancer. We set out to find new cancer immunotherapy targets by phenotypic screening on human regulatory T (Treg) cells and report the discovery of novel activators of tumor necrosis factor receptor 2 (TNFR2) and a potential role for this target in immunotherapy. A diverse phage display library was screened to find antibody mimetics with preferential binding to Treg cells, the most Treg-selective of which were all, without exception, found to bind specifically to TNFR2. A subset of these TNFR2 binders were found to agonise the receptor, inducing iκ-B degradation and NF-κB pathway signalling in vitro. TNFR2 was found to be expressed by tumor-infiltrating Treg cells, and to a lesser extent Teff cells, from three lung cancer patients, and a similar pattern was also observed in mice implanted with CT26 syngeneic tumors. In such animals, TNFR2-specific agonists inhibited tumor growth, enhanced tumor infiltration by CD8+ T cells and increased CD8+ T cell IFN-γ synthesis. Together, these data indicate a novel mechanism for TNF-α-independent TNFR2 agonism in cancer immunotherapy, and demonstrate the utility of target-agnostic screening in highlighting important targets during drug discovery.
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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.