Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment
Abstract The tumor microenvironment (TME) influences cancer cell metabolism and survival. However, how immune and stromal cells respond to metabolic stress in vivo, and how nutrient limitations affect therapy, remains poorly understood. Here, we introduce Dual Ribosome Profiling (DualRP) to simultan...
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Nature Portfolio
2025-05-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-59986-7 |
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| author | Daniela Aviles-Huerta Rossella Del Pizzo Alexander Kowar Ali Hyder Baig Giuliana Palazzo Ekaterina Stepanova Cinthia Claudia Amaya Ramirez Sara D’Agostino Edoardo Ratto Catarina Pechincha Nora Siefert Helena Engel Shangce Du Silvia Cadenas-De Miguel Beiping Miao Victor M. Cruz-Vilchez Karin Müller-Decker Ilaria Elia Chong Sun Wilhelm Palm Fabricio Loayza-Puch |
| author_facet | Daniela Aviles-Huerta Rossella Del Pizzo Alexander Kowar Ali Hyder Baig Giuliana Palazzo Ekaterina Stepanova Cinthia Claudia Amaya Ramirez Sara D’Agostino Edoardo Ratto Catarina Pechincha Nora Siefert Helena Engel Shangce Du Silvia Cadenas-De Miguel Beiping Miao Victor M. Cruz-Vilchez Karin Müller-Decker Ilaria Elia Chong Sun Wilhelm Palm Fabricio Loayza-Puch |
| author_sort | Daniela Aviles-Huerta |
| collection | DOAJ |
| description | Abstract The tumor microenvironment (TME) influences cancer cell metabolism and survival. However, how immune and stromal cells respond to metabolic stress in vivo, and how nutrient limitations affect therapy, remains poorly understood. Here, we introduce Dual Ribosome Profiling (DualRP) to simultaneously monitor translation and ribosome stalling in multiple tumor cell populations. DualRP reveals that cancer-fibroblast interactions trigger an inflammatory program that reduces amino acid shortages during glucose starvation. In immunocompetent mice, we show that serine and glycine are essential for optimal T cell function and that their deficiency impairs T cell fitness. Importantly, immune checkpoint blockade therapy imposes amino acid restrictions specifically in T cells, demonstrating that therapies create distinct metabolic demands across TME cell types. By mapping codon-resolved ribosome stalling in a cell‑type‑specific manner, DualRP uncovers metabolic crosstalk that shapes translational programs. DualRP thus offers a powerful, innovative approach for dissecting tumor cell metabolic interplay and guiding combined metabolic-immunotherapeutic strategies. |
| format | Article |
| id | doaj-art-a93ba6bf486044c2840e307edb2811ad |
| institution | DOAJ |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-05-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-a93ba6bf486044c2840e307edb2811ad2025-08-20T03:08:43ZengNature PortfolioNature Communications2041-17232025-05-0116111410.1038/s41467-025-59986-7Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironmentDaniela Aviles-Huerta0Rossella Del Pizzo1Alexander Kowar2Ali Hyder Baig3Giuliana Palazzo4Ekaterina Stepanova5Cinthia Claudia Amaya Ramirez6Sara D’Agostino7Edoardo Ratto8Catarina Pechincha9Nora Siefert10Helena Engel11Shangce Du12Silvia Cadenas-De Miguel13Beiping Miao14Victor M. Cruz-Vilchez15Karin Müller-Decker16Ilaria Elia17Chong Sun18Wilhelm Palm19Fabricio Loayza-Puch20Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Faculty of Biosciences, University of HeidelbergFaculty of Biosciences, University of HeidelbergFaculty of Biosciences, University of HeidelbergFaculty of Biosciences, University of HeidelbergImmune Regulation in Cancer, German Cancer Research Center (DKFZ)Department of Cellular and Molecular Medicine, KU LeuvenImmune Regulation in Cancer, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Core Facility Tumor Models, German Cancer Research Center (DKFZ)Department of Cellular and Molecular Medicine, KU LeuvenImmune Regulation in Cancer, German Cancer Research Center (DKFZ)Division of Cell Signaling and Metabolism, German Cancer Research Center (DKFZ)Translational Control and Metabolism, German Cancer Research Center (DKFZ)Abstract The tumor microenvironment (TME) influences cancer cell metabolism and survival. However, how immune and stromal cells respond to metabolic stress in vivo, and how nutrient limitations affect therapy, remains poorly understood. Here, we introduce Dual Ribosome Profiling (DualRP) to simultaneously monitor translation and ribosome stalling in multiple tumor cell populations. DualRP reveals that cancer-fibroblast interactions trigger an inflammatory program that reduces amino acid shortages during glucose starvation. In immunocompetent mice, we show that serine and glycine are essential for optimal T cell function and that their deficiency impairs T cell fitness. Importantly, immune checkpoint blockade therapy imposes amino acid restrictions specifically in T cells, demonstrating that therapies create distinct metabolic demands across TME cell types. By mapping codon-resolved ribosome stalling in a cell‑type‑specific manner, DualRP uncovers metabolic crosstalk that shapes translational programs. DualRP thus offers a powerful, innovative approach for dissecting tumor cell metabolic interplay and guiding combined metabolic-immunotherapeutic strategies.https://doi.org/10.1038/s41467-025-59986-7 |
| spellingShingle | Daniela Aviles-Huerta Rossella Del Pizzo Alexander Kowar Ali Hyder Baig Giuliana Palazzo Ekaterina Stepanova Cinthia Claudia Amaya Ramirez Sara D’Agostino Edoardo Ratto Catarina Pechincha Nora Siefert Helena Engel Shangce Du Silvia Cadenas-De Miguel Beiping Miao Victor M. Cruz-Vilchez Karin Müller-Decker Ilaria Elia Chong Sun Wilhelm Palm Fabricio Loayza-Puch Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment Nature Communications |
| title | Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment |
| title_full | Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment |
| title_fullStr | Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment |
| title_full_unstemmed | Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment |
| title_short | Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment |
| title_sort | dual ribosome profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment |
| url | https://doi.org/10.1038/s41467-025-59986-7 |
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