ArticleThe Journal of clinical investigation2009
PKCtheta is required for alloreactivity and GVHD but not for immune responses toward leukemia and infection in mice.
Article in The Journal of clinical investigation, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 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
54 citing papers in PubMed, 77 citations in OpenAlex.
- Protein kinase C theta: evolution, regulation, and function.The Biochemical journal · 2026Review
- Protein Kinase C Family: Structures, Biological Functions, Diseases, and Pharmaceutical Interventions.MedComm · 2025Review
- Identification of miRNA Associated withInternational journal of molecular sciences · 2023Article
- Bioinformatics and Raman spectroscopy-based identification of key pathways and genes enabling differentiation between acute myeloid leukemia and T cell acute lymphoblastic leukemia.Frontiers in immunology · 2023Article
- A MLR-Based Approach to Analyze Regulators of T Lymphocyte Activation In Vivo.International journal of molecular sciences · 2022Article
- Article
- The Emerging Function of PKCtheta in Cancer.Biomolecules · 2021Review
- Cell-Penetrating Anti-Protein Kinase C Theta Antibodies Act Intracellularly to Generate Stable, Highly Suppressive Regulatory T Cells.Molecular therapy : the journal of the American Society of Gene Therapy · 2020Article
- Article
- PRKCQ inhibition enhances chemosensitivity of triple-negative breast cancer by regulating Bim.Breast cancer research : BCR · 2020Article
- Thioredoxin-1 confines T cell alloresponse and pathogenicity in graft-versus-host disease.The Journal of clinical investigation · 2019Article
- Phosphotyrosine-dependent interaction between the kinases PKCθ and Zap70 promotes proximal TCR signaling.Science signaling · 2019Article
- Cymerus™ iPSC-MSCs significantly prolong survival in a pre-clinical, humanized mouse model of Graft-vs-host disease.Stem cell research · 2019Article
- DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.Nature communications · 2018Article
- Inhibition of the IRE-1α/XBP-1 pathway prevents chronic GVHD and preserves the GVL effect in mice.Blood advances · 2018Article
- Intracellular Delivery of Anti-pPKCθ (Thr538) via Protein Transduction Domain Mimics for Immunomodulation.Molecular therapy : the journal of the American Society of Gene Therapy · 2016Article
- PRKCQ promotes oncogenic growth and anoikis resistance of a subset of triple-negative breast cancer cells.Breast cancer research : BCR · 2016Article
- HDAC Inhibitors Enhance T-Cell Chemokine Expression and Augment Response to PD-1 Immunotherapy in Lung Adenocarcinoma.Clinical cancer research : an official journal of the American Association for Cancer Research · 2016Article
- Programmed death ligand-1 expression on donor T cells drives graft-versus-host disease lethality.The Journal of clinical investigation · 2016Article
- T-bet Promotes Acute Graft-versus-Host Disease by Regulating Recipient Hematopoietic Cells in Mice.Journal of immunology (Baltimore, Md. : 1950) · 2016Article
Corrections and comments
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Authors and funding
14 authors at 6 institutions in 1 country.
Funding
Abstract
When used as therapy for hematopoietic malignancies, allogeneic BM transplantation (BMT) relies on the graft-versus-leukemia (GVL) effect to eradicate residual tumor cells through immunologic mechanisms. However, graft-versus-host disease (GVHD), which is initiated by alloreactive donor T cells that recognize mismatched major and/or minor histocompatibility antigens and cause severe damage to hematopoietic and epithelial tissues, is a potentially lethal complication of allogeneic BMT. To enhance the therapeutic potential of BMT, we sought to find therapeutic targets that could inhibit GVHD while preserving GVL and immune responses to infectious agents. We show here that T cell responses triggered in mice by either Listeria monocytogenes or administration of antigen and adjuvant were relatively well preserved in the absence of PKC isoform theta (PKCtheta), a key regulator of TCR signaling. In contrast, PKCtheta was required for alloreactivity and GVHD induction. Furthermore, absence of PKCtheta raised the threshold for T cell activation, which selectively affected alloresponses. Most importantly, PKCtheta-deficient T cells retained the ability to respond to virus infection and to induce GVL effect after BMT. These findings suggest PKCtheta is a potentially unique therapeutic target required for GVHD induction but not for GVL or protective responses to infectious agents.
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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.