TY  - JOUR
AU  - Aviles-Huerta, Daniela
AU  - Del Pizzo, Rossella
AU  - Kowar, Alexander
AU  - Baig, Ali Hyder
AU  - Palazzo, Giuliana
AU  - Stepanova, Ekaterina
AU  - Amaya Ramirez, Cinthia Claudia
AU  - D'Agostino, Sara
AU  - Ratto, Edoardo
AU  - Pechincha, Catarina
AU  - Siefert, Nora Sophie
AU  - Engel, Helena
AU  - Du, Shangce
AU  - Cadenas-De Miguel, Silvia
AU  - Miao, Beiping
AU  - Cruz-Vilchez, Victor M
AU  - Müller-Decker, Karin
AU  - Elia, Ilaria
AU  - Sun, Chong
AU  - Palm, Wilhelm
AU  - Loayza-Puch, Fabricio
TI  - Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment.
JO  - Nature Communications
VL  - 16
IS  - 1
SN  - 2041-1723
CY  - [London]
PB  - Springer Nature
M1  - DKFZ-2025-01036
SP  - 4652
PY  - 2025
N1  - #EA:B250#LA:B250#
AB  - 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.
KW  - Tumor Microenvironment: immunology
KW  - Tumor Microenvironment: genetics
KW  - Animals
KW  - Ribosomes: metabolism
KW  - Ribosomes: genetics
KW  - Mice
KW  - Humans
KW  - Stromal Cells: metabolism
KW  - Neoplasms: metabolism
KW  - Neoplasms: pathology
KW  - Neoplasms: genetics
KW  - Neoplasms: immunology
KW  - Cell Line, Tumor
KW  - T-Lymphocytes: metabolism
KW  - T-Lymphocytes: immunology
KW  - Glycine: metabolism
KW  - Protein Biosynthesis
KW  - Amino Acids: metabolism
KW  - Mice, Inbred C57BL
KW  - Serine: metabolism
KW  - Female
KW  - Fibroblasts: metabolism
KW  - Ribosome Profiling
KW  - Glycine (NLM Chemicals)
KW  - Amino Acids (NLM Chemicals)
KW  - Serine (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:40389477
DO  - DOI:10.1038/s41467-025-59986-7
UR  - https://inrepo02.dkfz.de/record/301494
ER  -