Journal Article

DKFZ-2025-02301

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Intratumoral regulatory T cells are associated with treatment response to neoadjuvant chemotherapy and prognosis in gastroesophageal adenocarcinoma.

Baenke, F.DKFZ* ; Stammberger, A. ; Sommer, U. ; Brückmann, S. ; Merboth, F. ; Polster, H. ; Digomann, D.DKFZ* ; Natusch Bufe, L.DKFZ* ; Rupp, L. ; Aust, D. E. ; Weitz, J.DKFZ* ; Stange, D. E.DKFZ* ; Schmitz, M.DKFZ* ; Seifert, L.DKFZ* ; Seifert, A. M.DKFZ*

2025
Taylor & Franics Abingdon

Abstract: Gastroesophageal junction (GEJ) adenocarcinoma is an increasingly common cancer with complex biology and poor prognosis. The treatment strategy for locally advanced tumors involves multimodal treatment with perioperative chemotherapy. However, survival rates remain low, especially for advanced disease. Here, formalin-fixed paraffin-embedded tumor sections from 72 patients with GEJ I and II adenocarcinoma who underwent primary resection or perioperative standard-of-care FLOT treatment were analyzed for their intratumoral T cell composition using multiplex immunohistochemistry. The proportions of T cells and their influence on survival were evaluated using Mann-Whitney U and log rank analyses. A comparison of short- and long-term survivors revealed significant differences in the infiltration of regulatory T cells (Tregs). Tumors after neoadjuvant FLOT treatment presented increased proportions of CD8+ T cells with reduced Granzyme B expression, indicating an altered immune response. Overall survival analysis revealed that high infiltration of Tregs was associated with poor survival. Notably, responders to FLOT therapy had a greater T cell frequency and improved survival, whereas nonresponders presented higher levels of Tregs and CD8+ T cells expressing TIM-3. Overall, GEJ cancer patients had increased CD8+ T cells after neoadjuvant chemotherapy with FLOT, and Tregs were associated with treatment response and reduced survival.

Keyword(s): Humans (MeSH) ; Neoadjuvant Therapy (MeSH) ; Adenocarcinoma: immunology (MeSH) ; Adenocarcinoma: drug therapy (MeSH) ; Adenocarcinoma: pathology (MeSH) ; Adenocarcinoma: mortality (MeSH) ; Esophageal Neoplasms: immunology (MeSH) ; Esophageal Neoplasms: drug therapy (MeSH) ; Esophageal Neoplasms: pathology (MeSH) ; Esophageal Neoplasms: mortality (MeSH) ; Male (MeSH) ; T-Lymphocytes, Regulatory: immunology (MeSH) ; Female (MeSH) ; Middle Aged (MeSH) ; Stomach Neoplasms: immunology (MeSH) ; Stomach Neoplasms: drug therapy (MeSH) ; Stomach Neoplasms: pathology (MeSH) ; Stomach Neoplasms: mortality (MeSH) ; Aged (MeSH) ; Prognosis (MeSH) ; Esophagogastric Junction: pathology (MeSH) ; Esophagogastric Junction: immunology (MeSH) ; Lymphocytes, Tumor-Infiltrating: immunology (MeSH) ; Antineoplastic Combined Chemotherapy Protocols: therapeutic use (MeSH) ; CD8-Positive T-Lymphocytes: immunology (MeSH) ; Adult (MeSH) ; Hepatitis A Virus Cellular Receptor 2: metabolism (MeSH) ; Chemotherapy, Adjuvant (MeSH) ; Treatment Outcome (MeSH) ; GEJ adenocarcinoma ; Multiplex immunohistochemistry ; intratumoral T cells ; neoadjuvant chemotherapy ; Hepatitis A Virus Cellular Receptor 2

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Contributing Institute(s):

1. DKTK Koordinierungsstelle Dresden (DD01)

Research Program(s):

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

Appears in the scientific report 2025

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Database coverage:
; ; Article Processing Charges ; BIOSIS Previews ; Biological Abstracts ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; Essential Science Indicators ; Fees ; IF >= 5 ; JCR ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection

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