ArticleBlood2013
Pharmacologic inhibition of PKCα and PKCθ prevents GVHD while preserving GVL activity in mice.
Article in Blood, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 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
26 citing papers in PubMed, 39 citations in OpenAlex.
- PKC isoforms in hematopoietic lineages and myeloid/lymphoid leukemias: mechanistic insights and therapeutic prospects.Frontiers in oncology · 2026Review
- A MLR-Based Approach to Analyze Regulators of T Lymphocyte Activation In Vivo.International journal of molecular sciences · 2022Article
- Article
- Advances in Immunosuppressive Agents Based on Signal Pathway.Frontiers in pharmacology · 2022Review
- Proximal and distal effects of genetic susceptibility to multiple sclerosis on the T cell epigenome.Nature communications · 2021Article
- The Emerging Function of PKCtheta in Cancer.Biomolecules · 2021Review
- 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
- DOT1L inhibition attenuates graft-versus-host disease by allogeneic T cells in adoptive immunotherapy models.Nature communications · 2018Article
- Strategies for Enhancing and Preserving Anti-leukemia Effects Without Aggravating Graft-Versus-Host Disease.Frontiers in immunology · 2018Review
- Virotherapy as Potential Adjunct Therapy for Graft-Vs-Host Disease.Current pathobiology reports · 2018Review
- T-Cell Manipulation Strategies to Prevent Graft-Versus-Host Disease in Haploidentical Stem Cell Transplantation.Biomedicines · 2017Review
- Ceramide synthesis regulates T cell activity and GVHD development.JCI insight · 2017Article
- CD8(+) Tregs promote GVHD prevention and overcome the impaired GVL effect mediated by CD4(+) Tregs in mice.Oncoimmunology · 2016Article
- Metabolic reprogramming of alloantigen-activated T cells after hematopoietic cell transplantation.The Journal of clinical investigation · 2016Article
- Therapeutics for Graft-versus-Host Disease: From Conventional Therapies to Novel Virotherapeutic Strategies.Viruses · 2016Review
- MicroRNA-17-92 controls T-cell responses in graft-versus-host disease and leukemia relapse in mice.Blood · 2015Article
- Advances and challenges in immunotherapy for solid organ and hematopoietic stem cell transplantation.Science translational medicine · 2015Review
- Immunomodulation of Selective Naive T Cell Functions by p110δ Inactivation Improves the Outcome of Mismatched Cell Transplantation.Cell reports · 2015Article
- PKC-Theta in Regulatory and Effector T-cell Functions.Frontiers in immunology · 2015Review
Corrections and comments
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Authors and funding
15 authors at 5 institutions in 1 country.
Funding
Abstract
Allogeneic hematopoietic cell transplantation (HCT) is the most effective therapy for hematopoietic malignancies through T-cell-mediated graft-vs-leukemia (GVL) effects but often leads to severe graft-vs-host disease (GVHD). Given that protein kinase Cθ (PKCθ), in cooperation with PKCα, is essential for T-cell signaling and function, we have evaluated PKCθ and PKCα as potential therapeutic targets in allogeneic HCT using genetic and pharmacologic approaches. We found that the ability of PKCα(-/-)/θ(-/-) donor T cells to induce GVHD was further reduced compared with PKCθ(-/-) T cells in relation with the relevance of both isoforms to allogeneic donor T-cell proliferation, cytokine production, and migration to GVHD target organs. Treatment with a specific inhibitor for both PKCθ and PKCα impaired donor T-cell proliferation, migration, and chemokine/cytokine production and significantly decreased GVHD in myeloablative preclinical murine models of allogeneic HCT. Moreover, pharmacologic inhibition of PKCθ and PKCα spared T-cell cytotoxic function and GVL effects. Our findings indicate that PKCα and θ contribute to T-cell activation with overlapping functions essential for GVHD induction while less critical to the GVL effect. Thus, targeting PKCα and PKCθ signaling with pharmacologic inhibitors presents a therapeutic option for GVHD prevention while largely preserving the GVL activity in patients receiving HCT.
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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.