ArticleJCI insight2016
The MEK inhibitor trametinib separates murine graft-versus-host disease from graft-versus-tumor effects.
Article in JCI insight, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
17 citing papers in PubMed.
- The MEK1/2-IRF4 axis fosters T follicular helper cell differentiationand antitumor humoral immune response.Journal of translational medicine · 2026Article
- Trametinib Decreased Intracerebral Hemorrhages and Endothelial-to-Mesenchymal Transition in KRASStroke · 2026Article
- Article
- Interferon regulatory factor 4 plays a pivotal role in the development of aGVHD-associated colitis.Oncoimmunology · 2024Article
- Lymphocyte Depleting and Modulating Therapies for Chronic Lung Allograft Dysfunction.Pharmacological reviews · 2023Review
- Transcriptome analysis in acute gastrointestinal graft-Haematologica · 2023Article
- Dual inhibition of the MEK/ERK and PI3K/AKT pathways prevents pulmonary GVHD suppressing perivenulitis and bronchiolitis.Blood advances · 2023Article
- Kinase Inhibition as Treatment for Acute and Chronic Graft-Frontiers in immunology · 2021Review
- Kras-Deficient T Cells Attenuate Graft-versus-Host Disease but Retain Graft-versus-Leukemia Activity.Journal of immunology (Baltimore, Md. : 1950) · 2020Article
- The MEK Inhibitor Trametinib Suppresses Major Histocompatibility Antigen-mismatched Rejection Following Pancreatic Islet Transplantation.Transplantation direct · 2020Article
- PRMT5 regulates T cell interferon response and is a target for acute graft-versus-host disease.JCI insight · 2020Article
- Phosphorylated ERK1/2 in CD4 T cells is associated with acute GVHD in allogeneic hematopoietic stem cell transplantation.Blood advances · 2020Article
- New Approaches for the Treatment of Chronic Graft-Versus-Host Disease: Current Status and Future Directions.Frontiers in immunology · 2020Review
- The MEK Inhibitor Trametinib Ameliorates Kidney Fibrosis by Suppressing ERK1/2 and mTORC1 Signaling.Journal of the American Society of Nephrology : JASN · 2019Article
- MEK inhibition enhances oncolytic virus immunotherapy through increased tumor cell killing and T cell activation.Science translational medicine · 2018Article
- Current approaches to prevent and treat GVHD after allogeneic stem cell transplantation.Hematology. American Society of Hematology. Education Program · 2018Review
- Strategies for Enhancing and Preserving Anti-leukemia Effects Without Aggravating Graft-Versus-Host Disease.Frontiers in immunology · 2018Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The efficacy of allogeneic hematopoietic stem cell transplantation for hematologic malignancies is limited by the difficulty in suppressing graft-versus-host disease (GVHD) without compromising graft-versus-tumor (GVT) effects. We previously showed that RAS/MEK/ERK signaling depends on memory differentiation in human T cells, which confers susceptibility to selective inhibition of naive T cells. Actually, antineoplastic MEK inhibitors selectively suppress alloreactive T cells, sparing virus-specific T cells in vitro. Here, we show that trametinib, a MEK inhibitor clinically approved for melanoma, suppresses GVHD safely without affecting GVT effects in vivo. Trametinib prolonged survival of GVHD mice and attenuated GVHD symptoms and pathology in the gut and skin. It inhibited ERK1/2 phosphorylation and expansion of donor T cells, sparing Tregs and B cells. Although high-dose trametinib inhibited myeloid cell engraftment, low-dose trametinib suppressed GVHD without severe adverse events. Notably, trametinib facilitated the survival of mice transplanted with allogeneic T cells and P815 tumor cells with no residual P815 cells observed in the livers and spleens, whereas tacrolimus resulted in P815 expansion. These results confirm that trametinib selectively suppresses GVHD-inducing T cells while sparing antitumor T cells in vivo, which makes it a promising candidate for translational studies aimed at preventing or treating GVHD.
Indexed as
Identifiers
What OpenQuestion holds
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.