TY  - JOUR
AU  - Barroux, Melissa
AU  - Househam, Jacob
AU  - Lakatos, Eszter
AU  - Ronel, Tahel
AU  - Baker, Ann-Marie
AU  - Salié, Henrike
AU  - Mossner, Maximilian
AU  - Smith, Kane
AU  - Kimberley, Chris
AU  - Nowinski, Salpie
AU  - Berner, Alison
AU  - Gunasri, Vinaya
AU  - Borgmann, Martin
AU  - Liffers, Sven
AU  - Jansen, Marnix
AU  - Caravagna, Giulio
AU  - Steiger, Katja
AU  - Slotta-Huspenina, Julia
AU  - Weichert, Wilko
AU  - Zapata, Luis
AU  - Giota, Eleftheria
AU  - Lorenzen, Sylvie
AU  - Alberstmeier, Markus
AU  - Chain, Benny
AU  - Friess, Helmut
AU  - Bengsch, Bertram
AU  - Schmid, Roland M
AU  - Siveke, Jens
AU  - Quante, Michael
AU  - Graham, Trevor A
TI  - Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma.
JO  - Nature cancer
VL  - 6
IS  - 5
SN  - 2662-1347
CY  - London
PB  - Nature Research
M1  - DKFZ-2025-00987
SP  - 820-837
PY  - 2025
N1  - 2025 May;6(5):820-837
AB  - Locally advanced esophageal adenocarcinoma remains difficult to treat and the ecological and evolutionary dynamics responsible for resistance and recurrence are incompletely understood. Here, we performed longitudinal multiomic analysis of patients with esophageal adenocarcinoma in the MEMORI trial. Multi-region multi-timepoint whole-exome and paired transcriptome sequencing was performed on 27 patients before, during and after neoadjuvant treatment. We found major transcriptomic changes during treatment with upregulation of immune, stromal and oncogenic pathways. Genetic data revealed that clonal sweeps through treatment were rare. Imaging mass cytometry and T cell receptor sequencing revealed remodeling of the tumor microenvironment during treatment. The presence of genetic immune escape, a less-cytotoxic T cell phenotype and a lack of clonal T cell expansions were linked to poor treatment response. In summary, there were widespread transcriptional and environmental changes through treatment, with limited clonal replacement, suggestive of phenotypic plasticity.
LB  - PUB:(DE-HGF)16
C6  - pmid:40369175
DO  - DOI:10.1038/s43018-025-00955-w
UR  - https://inrepo02.dkfz.de/record/301315
ER  -