Journal Article

DKFZ-2025-00987

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Evolutionary and immune microenvironment dynamics during neoadjuvant treatment of esophageal adenocarcinoma.

Barroux, M.DKFZ* ; Househam, J. ; Lakatos, E. ; Ronel, T. ; Baker, A.-M. ; Salié, H. ; Mossner, M. ; Smith, K. ; Kimberley, C. ; Nowinski, S. ; Berner, A. ; Gunasri, V. ; Borgmann, M. ; Liffers, S.DKFZ* ; Jansen, M. ; Caravagna, G. ; Steiger, K. ; Slotta-Huspenina, J. ; Weichert, W. ; Zapata, L. ; Giota, E. ; Lorenzen, S. ; Alberstmeier, M. ; Chain, B. ; Friess, H. ; Bengsch, B.DKFZ* ; Schmid, R. M.DKFZ* ; Siveke, J.DKFZ* ; Quante, M.DKFZ* ; Graham, T. A.

2025
Nature Research London

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Please use a persistent id in citations: doi:10.1038/s43018-025-00955-w

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.

Note: 2025 May;6(5):820-837

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Contributing Institute(s):

1. DKTK Koordinierungsstelle München (MU01)
2. DKTK Koordinierungsstelle Essen/Düsseldorf (ED01)
3. DKTK Koordinierungsstelle Freiburg (FR01)

Research Program(s):

1. 899 - ohne Topic (POF4-899) (POF4-899)

Appears in the scientific report 2025

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; Current Contents - Clinical Medicine ; DEAL Nature ; Essential Science Indicators ; IF >= 20 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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