ArticleGut2026
Targeting MLCK1 uncouples immune checkpoint inhibitor-induced colitis from antitumour immunity.
Article in Gut, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
5 citing papers in PubMed.
- Review
- Dysbiosis-Associated Lysophosphatidic Acid Primes Immune Checkpoint Inhibitor-Induced Intestinal Barrier Dysfunction via the Lysophosphatidic Acid Receptor 2-Myosin Light Chain Kinase Axis.Cellular and molecular gastroenterology and hepatology · 2026Article
- Microbiota and immune-related adverse events in cancer immunotherapy.Nature reviews. Cancer · 2026Review
- Deconstructing cancer in 3D: models, mechanisms, and personalized solutions.Molecular cancer · 2026Review
- Food-derived molecules as regulators of intestinal tight junctions and barrier function: mechanisms and implications.Frontiers in drug delivery · 2026Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
36 authors.
Funding
Abstract
objectiveImmune checkpoint inhibitors (ICIs) have revolutionised cancer treatment and patients' survival. However, ICIs also cause severe immune-related adverse events, notably colitis, resulting in ICIs therapy discontinuation and tumour immunotherapy failure. This study investigates long myosin light chain kinase 1 (MLCK1), a known regulator of tight junction and gut permeability, to elucidate the mechanisms underlying ICI-mediated colitis and identify approaches to reduce this toxicity.
designThis study employed an integrated approach, using clinical samples, in vivo models and in vitro organoid systems. Biopsies from patients with ICIs colitis were profiled using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics. To recapitulate human ICIs colitis, we used a wild mouse microbiota (WildR) model, alongside various genetically modified and tumour-bearing models (including melanoma and MC38). Furthermore, mechanisms were investigated through organoid-immune cell co-cultures. Finally, surface plasmon resonance, microscale thermophoresis, full-spectrum flow cytometry, bulk RNA sequencing, immunostaining, ELISA and gut permeability assays were performed to comprehensively delineate the underlying molecular mechanism.
resultsTight junction integrity was compromised in both human ICIs colitis and our WildR mouse model. We determined that this barrier dysfunction is driven by activation of the MLCK1-mediated leak pathway following ICI treatment. Using murine models, we identified tumour necrosis factor secreted by CD8
conclusionsThese findings suggest that MLCK1-dependent tight junction regulation is essential for ICIs colitis, positioning barrier restoration as a potential therapeutic strategy.
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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.