ArticleNature2019
Structure of the IFNγ receptor complex guides design of biased agonists.
Article in Nature, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT05699577 (Prognostic Value of Some Biochemical Markers in Breast Cancer), which is not on this map. Cited by 85 papers, 1 of them a synthesis that pooled it.
What it found
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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.
Prognostic Value of Some Biochemical Markers in Breast Cancer
Who cites it
85 citing papers in PubMed, 1 synthesis or guideline pooled it, 136 citations in OpenAlex.
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- Identification and characterization of bone marrow plasma cells producing IFN-γ-neutralizing autoantibodies in adult-onset immunodeficiency.Cell reports. Medicine · 2026Article
- Interferon signaling pathways in health and disease.Molecular biomedicine · 2025Review
- Association between soluble immune mediators and outcomes in patients with unresectable stage III non-small cell lung cancer treated with concurrent chemoradiotherapy followed by durvalumab.Translational lung cancer research · 2025Article
- Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling.bioRxiv : the preprint server for biology · 2025Article
- The difference in tumor immune microenvironment and IFN-γ response between solid and non-solid adenocarcinoma.Translational lung cancer research · 2025Article
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- Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.Nature communications · 2025Article
- The effects of bone marrow humoral components of B-cell acute lymphoblastic leukemia patients on natural killer cell suppression.Immunologic research · 2025Article
- Dual regulation of gastrointestinal tumor progression by the IFN-γ/STAT1 pathway and prospects for targeted therapy.Frontiers in oncology · 2025Review
- IFN-gamma in the tumor microenvironment: dual roles in cancer progression and therapy.EXCLI journal · 2025Review
25 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 4 institutions in 2 countries.
Funding
Abstract
The cytokine interferon-γ (IFNγ) is a central coordinator of innate and adaptive immunity, but its highly pleiotropic actions have diminished its prospects for use as an immunotherapeutic agent. Here, we took a structure-based approach to decoupling IFNγ pleiotropy. We engineered an affinity-enhanced variant of the ligand-binding chain of the IFNγ receptor IFNγR1, which enabled us to determine the crystal structure of the complete hexameric (2:2:2) IFNγ-IFNγR1-IFNγR2 signalling complex at 3.25 Å resolution. The structure reveals the mechanism underlying deficits in IFNγ responsiveness in mycobacterial disease syndrome resulting from a T168N mutation in IFNγR2, which impairs assembly of the full signalling complex. The topology of the hexameric complex offers a blueprint for engineering IFNγ variants to tune IFNγ receptor signalling output. Unexpectedly, we found that several partial IFNγ agonists exhibited biased gene-expression profiles. These biased agonists retained the ability to induce upregulation of major histocompatibility complex class I antigen expression, but exhibited impaired induction of programmed death-ligand 1 expression in a wide range of human cancer cell lines, offering a route to decoupling immunostimulatory and immunosuppressive functions of IFNγ for therapeutic applications.
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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.