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Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment

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 mo...

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Main Authors: Avilés Huerta, Daniela (Author) , Del Pizzo, Rossella (Author) , Kowar, Alexander (Author) , Baig, Ali Hyder (Author) , Palazzo, Giuliana (Author) , Stepanova, Ekaterina (Author) , Amaya Ramirez, Cinthia Claudia (Author) , D'Agostino, Sara (Author) , Ratto, Edoardo (Author) , Pechincha, Catarina (Author) , Siefert, Nora (Author) , Engel, Helena (Author) , Du, Shangce (Author) , Cadenas-De Miguel, Silvia (Author) , Miao, Beiping (Author) , Cruz-Vilchez, Victor M. (Author) , Müller-Decker, Karin (Author) , Elia, Ilaria (Author) , Sun, Chong (Author) , Palm, Wilhelm (Author) , Loayza-Puch, Fabricio (Author)
Format: Article (Journal)
Language:English
Published: 19 May 2025
In: Nature Communications
Year: 2025, Volume: 16, Pages: 1-14
ISSN:2041-1723
DOI:10.1038/s41467-025-59986-7
Online Access:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41467-025-59986-7
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41467-025-59986-7
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Author Notes: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
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Summary: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.
Item Description:Gesehen am 22.10.2025
Physical Description:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-025-59986-7

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