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@ARTICLE{Barroux:301315,
author = {M. Barroux$^*$ and J. Househam and E. Lakatos and T. Ronel
and A.-M. Baker and H. Salié and M. Mossner and K. Smith
and C. Kimberley and S. Nowinski and A. Berner and V.
Gunasri and M. Borgmann and S. Liffers$^*$ and M. Jansen and
G. Caravagna and K. Steiger and J. Slotta-Huspenina and W.
Weichert and L. Zapata and E. Giota and S. Lorenzen and M.
Alberstmeier and B. Chain and H. Friess and B. Bengsch$^*$
and R. M. Schmid$^*$ and J. Siveke$^*$ and M. Quante$^*$ and
T. A. Graham},
title = {{E}volutionary and immune microenvironment dynamics during
neoadjuvant treatment of esophageal adenocarcinoma.},
journal = {Nature cancer},
volume = {6},
number = {5},
issn = {2662-1347},
address = {London},
publisher = {Nature Research},
reportid = {DKFZ-2025-00987},
pages = {820-837},
year = {2025},
note = {2025 May;6(5):820-837},
abstract = {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.},
cin = {MU01 / ED01 / FR01},
ddc = {610},
cid = {I:(DE-He78)MU01-20160331 / I:(DE-He78)ED01-20160331 /
I:(DE-He78)FR01-20160331},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:40369175},
doi = {10.1038/s43018-025-00955-w},
url = {https://inrepo02.dkfz.de/record/301315},
}