ArticleJCI insight2017
Requirement of Treg-intrinsic CTLA4/PKCη signaling pathway for suppressing tumor immunity.
Article in JCI insight, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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.
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Who cites it
22 citing papers in PubMed, 29 citations in OpenAlex.
- Combination of radiotherapy and ICIs in advanced hepatocellular carcinoma: A systematic review of current evidence and future prospects (Review).Oncology letters · 2025Review
- ITGB7 Remodels Inflammation and Immune Microenvironment and Enhances Checkpoint Inhibitor-Based Immunotherapy in Pancreatic Cancer.Journal of inflammation research · 2025Article
- Exploring the impact of cuproptosis on prostate cancer prognosisFrontiers in pharmacology · 2025Article
- Single-Cell Analysis Uncovers Striking Cellular Heterogeneity of Lung-Infiltrating Regulatory T Cells during Eosinophilic versus Neutrophilic Allergic Airway Inflammation.Journal of immunology (Baltimore, Md. : 1950) · 2024Article
- Low expression of PRRG2 in kidney renal clear cell carcinoma: an immune infiltration-associated prognostic biomarker.Discover oncology · 2024Article
- Article
- Protein Kinase C at the Crossroad of Mutations, Cancer, Targeted Therapy and Immune Response.Biology · 2023Review
- High MICAL1 expression correlates with cancer progression and immune infiltration in renal clear cell carcinoma.BMC cancer · 2022Article
- Current Understanding of Cytotoxic T Lymphocyte Antigen-4 (CTLA-4) Signaling in T-Cell Biology and Disease Therapy.Molecules and cells · 2022Review
- Overarching roles of diacylglycerol signaling in cancer development and antitumor immunity.Science signaling · 2022Review
- Global evolution of the tumor microenvironment associated with progression from preinvasive invasive to invasive human lung adenocarcinoma.Cell reports · 2022Article
- Leveraging the Treg-intrinsic CTLA4-PKCη signaling pathway for cancer immunotherapy.Journal for immunotherapy of cancer · 2021Article
- Review
- Biological and molecular studies on specific immune cells treated with checkpoint inhibitors for the thera-personal approach of breast cancer patients (Oncology research · 2021Article
- Modulation of regulatory T cell function and stability by co-inhibitory receptors.Nature reviews. Immunology · 2020Review
- MKL-1 is a coactivator for STAT5b, the regulator of Treg cell development and function.Cell communication and signaling : CCS · 2020Article
- Protein Kinase C-η Deficiency Does Not Impair Antiviral Immunity and CD8Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- Requirement of Mitochondrial Transcription Factor A in Tissue-Resident Regulatory T Cell Maintenance and Function.Cell reports · 2019Article
- Combining Immune Checkpoint Inhibitors: Established and Emerging Targets and Strategies to Improve Outcomes in Melanoma.Frontiers in immunology · 2019Review
- Deciphering Key Pharmacological Pathways of Qingdai Acting on Chronic Myeloid Leukemia Using a Network Pharmacology-Based Strategy.Medical science monitor : international medical journal of experimental and clinical research · 2018Article
Corrections and comments
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
Abstract
The ability of Tregs to control the development of immune responses is essential for maintaining immune system homeostasis. However, Tregs also inhibit the development of efficient antitumor responses. Here, we explored the characteristics and mechanistic basis of the Treg-intrinsic CTLA4/PKCη signaling pathway that we recently found to be required for contact-dependent Treg-mediated suppression. We show that PKCη is required for the Treg-mediated suppression of tumor immunity in vivo. The presence of PKCη-deficient (Prkch-/-) Tregs in the tumor microenvironment was associated with a significantly increased expression of the costimulatory molecule CD86 on intratumoral CD103+ DCs, enhanced priming of antigen-specific CD8+ T cells, and greater levels of effector cytokines produced by these cells. Similar to mouse Tregs, the GIT/PAK/PIX complex also operated downstream of CTLA4 and PKCη in human Tregs, and GIT2 knockdown in Tregs promoted antitumor immunity. Collectively, our data suggest that targeting the CTLA4/PKCη/GIT/PAK/PIX signaling pathway in Tregs could represent a novel immunotherapeutic strategy to alleviate the negative impact of Tregs on antitumor immune responses.
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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.