biostudies-literatureCui KNational Natural Science Foundation of China (National Science Foundation of China)756-770https://www.ebi.ac.uk/biostudies/studies/S-EPMC12449461biostudies-literatureUnknown133(6)<h4>Background</h4>Hyperactive 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.<h4>Methods</h4>We 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.<h4>Results</h4>Ribosome inhibition elevated lymphoid cell cytotoxic granule secretion and macrophage pro-inflammation reprogrBritish journal of cancerTargeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.PMC124494618230311582472671T2250710184Wan QCui KZhu YLu XWang CLi QGong ZZhang QTang HZhang YLiu BGong LShen RfalseTargeting ribosomes reprograms the tumour microenvironment and augments cancer immunotherapy.<h4>Background</h4>Hyperactive 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.<h4>Methods</h4>We 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.<h4>Results</h4>Ribosome inhibition elevated lymphoid cell cytotoxic granule secretion and macrophage pro-inflammation reprogr2025-01-01T00:00:00Z2025 Oct2026-07-15T05:55:38.994Z2026-06-30T03:16:26.749ZS-EPMC124494614064628710.1038/s41416-025-03109-y