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@ARTICLE{AvilesHuerta:301494,
author = {D. Aviles-Huerta$^*$ and R. Del Pizzo$^*$ and A. Kowar$^*$
and A. H. Baig$^*$ and G. Palazzo$^*$ and E. Stepanova$^*$
and C. C. Amaya Ramirez$^*$ and S. D'Agostino$^*$ and E.
Ratto$^*$ and C. Pechincha$^*$ and N. S. Siefert$^*$ and H.
Engel$^*$ and S. Du$^*$ and S. Cadenas-De Miguel and B.
Miao$^*$ and V. M. Cruz-Vilchez$^*$ and K.
Müller-Decker$^*$ and I. Elia and C. Sun$^*$ and W.
Palm$^*$ and F. Loayza-Puch$^*$},
title = {{D}ual {R}ibosome {P}rofiling reveals metabolic limitations
of cancer and stromal cells in the tumor microenvironment.},
journal = {Nature Communications},
volume = {16},
number = {1},
issn = {2041-1723},
address = {[London]},
publisher = {Springer Nature},
reportid = {DKFZ-2025-01036},
pages = {4652},
year = {2025},
note = {#EA:B250#LA:B250#},
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.},
keywords = {Tumor Microenvironment: immunology / Tumor
Microenvironment: genetics / Animals / Ribosomes: metabolism
/ Ribosomes: genetics / Mice / Humans / Stromal Cells:
metabolism / Neoplasms: metabolism / Neoplasms: pathology /
Neoplasms: genetics / Neoplasms: immunology / Cell Line,
Tumor / T-Lymphocytes: metabolism / T-Lymphocytes:
immunology / Glycine: metabolism / Protein Biosynthesis /
Amino Acids: metabolism / Mice, Inbred C57BL / Serine:
metabolism / Female / Fibroblasts: metabolism / Ribosome
Profiling / Glycine (NLM Chemicals) / Amino Acids (NLM
Chemicals) / Serine (NLM Chemicals)},
cin = {B250 / A330 / D250 / W420},
ddc = {500},
cid = {I:(DE-He78)B250-20160331 / I:(DE-He78)A330-20160331 /
I:(DE-He78)D250-20160331 / I:(DE-He78)W420-20160331},
pnm = {312 - Funktionelle und strukturelle Genomforschung
(POF4-312)},
pid = {G:(DE-HGF)POF4-312},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40389477},
doi = {10.1038/s41467-025-59986-7},
url = {https://inrepo02.dkfz.de/record/301494},
}