Journal Article

DKFZ-2025-01036

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Dual Ribosome Profiling reveals metabolic limitations of cancer and stromal cells in the tumor microenvironment.

Aviles-Huerta, D. (First author)DKFZ* ; Del Pizzo, R. (First author)DKFZ* ; Kowar, A.DKFZ* ; Baig, A. H.DKFZ* ; Palazzo, G.DKFZ* ; Stepanova, E.DKFZ* ; Amaya Ramirez, C. C.DKFZ* ; D'Agostino, S.DKFZ* ; Ratto, E.DKFZ* ; Pechincha, C.DKFZ* ; Siefert, N. S.DKFZ* ; Engel, H.DKFZ* ; Du, S.DKFZ* ; Cadenas-De Miguel, S. ; Miao, B.DKFZ* ; Cruz-Vilchez, V. M.DKFZ* ; Müller-Decker, K.DKFZ* ; Elia, I. ; Sun, C.DKFZ* ; Palm, W.DKFZ* ; Loayza-Puch, F. (Last author)DKFZ*

2025
Springer Nature [London]

This record in other databases:  

Please use a persistent id in citations: doi:10.1038/s41467-025-59986-7

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.

Keyword(s): Tumor Microenvironment: immunology (MeSH) ; Tumor Microenvironment: genetics (MeSH) ; Animals (MeSH) ; Ribosomes: metabolism (MeSH) ; Ribosomes: genetics (MeSH) ; Mice (MeSH) ; Humans (MeSH) ; Stromal Cells: metabolism (MeSH) ; Neoplasms: metabolism (MeSH) ; Neoplasms: pathology (MeSH) ; Neoplasms: genetics (MeSH) ; Neoplasms: immunology (MeSH) ; Cell Line, Tumor (MeSH) ; T-Lymphocytes: metabolism (MeSH) ; T-Lymphocytes: immunology (MeSH) ; Glycine: metabolism (MeSH) ; Protein Biosynthesis (MeSH) ; Amino Acids: metabolism (MeSH) ; Mice, Inbred C57BL (MeSH) ; Serine: metabolism (MeSH) ; Female (MeSH) ; Fibroblasts: metabolism (MeSH) ; Ribosome Profiling (MeSH) ; Glycine ; Amino Acids ; Serine

Note: #EA:B250#LA:B250#

---

Contributing Institute(s):

1. B250 NWG Translationskontrolle und Stoffwechsel (B250)
2. A330 NWG Signaltransduktion und Stoffwechsel der Zelle (A330)
3. NWG Krebs-Immunregulation (D250)
4. Gruppe Müller-Decker (W420)

Research Program(s):

1. 312 - Funktionelle und strukturelle Genomforschung (POF4-312) (POF4-312)

Appears in the scientific report 2025

---

Database coverage:
; ; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; DOAJ Seal ; Essential Science Indicators ; Fees ; IF >= 15 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

---