ArticleNature immunology2014
Protein kinase C-η controls CTLA-4-mediated regulatory T cell function.
Article in Nature immunology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 96 papers, 1 of them a synthesis that pooled it.
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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
96 citing papers in PubMed, 1 synthesis or guideline pooled it, 134 citations in OpenAlex.
- In or out of control: Modulating regulatory T cell homeostasis and function with immune checkpoint pathways.Frontiers in immunology · 2022Pooled it
- Costimulation loss enhances IL-2-driven Treg generation by PI3K-STAT3 inhibition in CNS autoimmunity.EMBO molecular medicine · 2026Article
- The Treg-cell death axis in lung cancer: implications for immune evasion and novel therapeutic strategies.Molecular cancer · 2026Review
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- The role of coinhibitory receptor-expressing non-T cells in inflammation and immunity: unsung heroes or peripheral players?Experimental & molecular medicine · 2025Review
- Regulation of microtubule nucleation in glioblastoma cells by ARF GTPase-activating proteins GIT1 and GIT2 and protein kinase C.Cancer cell international · 2025Article
- Dermatotoxicity of Immune Checkpoint Inhibitors in Advanced Non-Small Cell Lung Cancer: Current Advances in Mechanistic Insights and Predictive Biomarker Identification.Cancer management and research · 2025Review
- Expanding the immunotherapy universe in extensive-stage small cell lung cancer: from chemoimmunotherapy backbone to next-wave combinations.Frontiers in immunology · 2025Review
- Immunotherapy for precision medicine in colorectal cancer.Expert review of precision medicine and drug development · 2025Article
- CTLA-4 expressing innate lymphoid cells modulate mucosal homeostasis in a microbiota dependent manner.Nature communications · 2024Article
- PKCActa pharmaceutica Sinica. B · 2024Article
- Mechanistic Insights into the Inhibition of a Common CTLA-4 Gene Mutation in the Cytoplasmic Domain.Molecules (Basel, Switzerland) · 2024Article
- Anti-CTLA-4 nanobody as a promising approach in cancer immunotherapy.Cell death & disease · 2024Review
- Role of Treg cell subsets in cardiovascular disease pathogenesis and potential therapeutic targets.Frontiers in immunology · 2024Review
- Immune checkpoint inhibitors and cancer immunotherapy by aptamers: an overview.Medical oncology (Northwood, London, England) · 2023Review
- Insights from a 30-year journey: function, regulation and therapeutic modulation of PD1.Nature reviews. Immunology · 2023Review
- De novo priming: driver of immunotherapy responses or epiphenomenon?Essays in biochemistry · 2023Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- Altered Lnc-EGFR, SNHG1, and LincRNA-Cox2 Profiles in Patients with Relapsing-Remitting Multiple Sclerosis: Impact on Disease Activity and Progression.Diagnostics (Basel, Switzerland) · 2023Article
- Experimental Melanoma Immunotherapy Model Using Tumor Vaccination with a Hematopoietic Cytokine.Journal of visualized experiments : JoVE · 2023Article
36 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 4 institutions in 3 countries.
Funding
Abstract
Regulatory T (Treg) cells, which maintain immune homeostasis and self-tolerance, form an immunological synapse (IS) with antigen-presenting cells (APCs). However, signaling events at the Treg cell IS remain unknown. Here we show that the kinase PKC-η associated with CTLA-4 and was recruited to the Treg cell IS. PKC-η-deficient Treg cells displayed defective suppressive activity, including suppression of tumor immunity but not of autoimmune colitis. Phosphoproteomic and biochemical analysis revealed an association between CTLA-4-PKC-η and the GIT2-αPIX-PAK complex, an IS-localized focal adhesion complex. Defective activation of this complex in PKC-η-deficient Treg cells was associated with reduced depletion of CD86 from APCs by Treg cells. These results reveal a CTLA-4-PKC-η signaling axis required for contact-dependent suppression and implicate this pathway as a potential cancer immunotherapy target.
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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.