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024 7 _ |a 10.1038/s41467-025-59986-7
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037 _ _ |a DKFZ-2025-01036
041 _ _ |a English
082 _ _ |a 500
100 1 _ |a Aviles-Huerta, Daniela
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245 _ _ |a Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment.
260 _ _ |a [London]
|c 2025
|b Springer Nature
336 7 _ |a article
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336 7 _ |a ARTICLE
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520 _ _ |a 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.
536 _ _ |a 312 - Funktionelle und strukturelle Genomforschung (POF4-312)
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650 _ 7 |a Glycine
|0 TE7660XO1C
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650 _ 7 |a Amino Acids
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650 _ 7 |a Serine
|0 452VLY9402
|2 NLM Chemicals
650 _ 2 |a Tumor Microenvironment: immunology
|2 MeSH
650 _ 2 |a Tumor Microenvironment: genetics
|2 MeSH
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Ribosomes: metabolism
|2 MeSH
650 _ 2 |a Ribosomes: genetics
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Humans
|2 MeSH
650 _ 2 |a Stromal Cells: metabolism
|2 MeSH
650 _ 2 |a Neoplasms: metabolism
|2 MeSH
650 _ 2 |a Neoplasms: pathology
|2 MeSH
650 _ 2 |a Neoplasms: genetics
|2 MeSH
650 _ 2 |a Neoplasms: immunology
|2 MeSH
650 _ 2 |a Cell Line, Tumor
|2 MeSH
650 _ 2 |a T-Lymphocytes: metabolism
|2 MeSH
650 _ 2 |a T-Lymphocytes: immunology
|2 MeSH
650 _ 2 |a Glycine: metabolism
|2 MeSH
650 _ 2 |a Protein Biosynthesis
|2 MeSH
650 _ 2 |a Amino Acids: metabolism
|2 MeSH
650 _ 2 |a Mice, Inbred C57BL
|2 MeSH
650 _ 2 |a Serine: metabolism
|2 MeSH
650 _ 2 |a Female
|2 MeSH
650 _ 2 |a Fibroblasts: metabolism
|2 MeSH
650 _ 2 |a Ribosome Profiling
|2 MeSH
700 1 _ |a Del Pizzo, Rossella
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700 1 _ |a Kowar, Alexander
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700 1 _ |a Baig, Ali Hyder
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700 1 _ |a Palazzo, Giuliana
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700 1 _ |a Stepanova, Ekaterina
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700 1 _ |a Amaya Ramirez, Cinthia Claudia
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700 1 _ |a D'Agostino, Sara
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700 1 _ |a Ratto, Edoardo
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700 1 _ |a Pechincha, Catarina
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700 1 _ |a Siefert, Nora Sophie
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700 1 _ |a Du, Shangce
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700 1 _ |a Cadenas-De Miguel, Silvia
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700 1 _ |a Cruz-Vilchez, Victor M
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700 1 _ |a Müller-Decker, Karin
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700 1 _ |a Elia, Ilaria
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700 1 _ |a Sun, Chong
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700 1 _ |a Palm, Wilhelm
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700 1 _ |a Loayza-Puch, Fabricio
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773 _ _ |a 10.1038/s41467-025-59986-7
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