ArticleBritish journal of cancer2025
Targeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.
Article in British journal of cancer, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Metabolic licensing of quiescent glioblastoma activation and immune evasion via astrocyte-mitochondria shuttle.Nature communications · 2026Article
- Druggable β-catenin palmitoyl-switch coordinates immune evasion via immunogenic ferroptosis resistance and PD-L1-mediated immunosuppression.Cell reports. Medicine · 2026Article
- Ribosome Biogenesis and Translational Control in Skeletal Muscle Atrophy and Hypertrophy: Mechanisms and Therapeutic Perspectives.Biomolecules · 2026Review
- Article
- Leveraging single-cell foundation models for accurate survival outcome prediction.Bioinformatics advances · 2026Article
- Targeting RNA polymerase I to boost natural killer cell anticancer activity in multiple myeloma.Cell death & disease · 2025Article
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Authors and funding
13 authors.
Funding
Abstract
backgroundHyperactive ribosome biogenesis is a hallmark of tumours. Current ribosome-related studies are concentrated on cancer cells. Ribosomes can regulate both tumour and non-cancer cells within the tumour microenvironment, yet the immunomodulatory effects of cellular ribosome biogenesis blockade remain inadequately understood.
methodsWe performed ribosome-targeting therapy utilizing CX-5461, an effective and acknowledged selective inhibitor of ribosome biogenesis, in immunocompetent in vivo models and submitted for single-cell RNA sequencing (scRNA-seq). Additional large-scale human scRNA-seq data, in-house clinical samples and assays were used.
resultsRibosome inhibition elevated lymphoid cell cytotoxic granule secretion and macrophage pro-inflammation reprogramming. We uncovered unique immune cell subpopulations that are sensitive to ribosome biogenesis blockade and are associated with adverse clinical outcomes. Impressively, these cells regress during responsive immune checkpoint blockade (ICB) treatment, revealing that they are essential for immunotherapy efficacy. Moreover, targeting ribosomes induces immune checkpoint expression (such as Lag3) and significantly sensitizes tumours to anti-Lag3 immunotherapy, eliciting potent tumour regression and deeper anti-tumour immune responses.
conclusionsThese findings unravel previously unrecognized roles of cellular ribosome biogenesis in sustaining immunosuppressive non-cancer cells. Our work unveils that ribosome biogenesis blockade could reinstate immunosurveillance and provide novel strategies to enhance the ICB efficacy in patients with poor immunogenicity.
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