Intratumoral dendritic cells and T cells predict survival in gastroenteropancreatic neuroendocrine neoplasms

in Endocrine-Related Cancer
Authors:
Wiebke Werner Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Katharina Detjen Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Alix Bruneau Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Isabella Lurje Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Natalie Nestel Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Henning Jann Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Frank Tacke Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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https://orcid.org/0000-0001-6206-0226
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Bertram Wiedenmann Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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Christoph Roderburg Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany
Clinic for Gastroenterology, Hepatology and Infectious Diseases, University Hospital Düsseldorf, Medical Faculty of Heinrich Heine, University Düsseldorf, Düsseldorf, Germany

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Linda Hammerich Department of Hepatology and Gastroenterology, Charité Universitaetsmedizin Berlin, Campus Virchow-Klinikum and Campus Charité Mitte, Berlin, Germany

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https://orcid.org/0000-0003-0557-3927

Correspondence should be addressed to L Hammerich: linda.hammerich@charite.de
DOI:
https://doi.org/10.1530/ERC-22-0357
Volume/Issue:
Volume 30: Issue 7
Article Type:
Research Article
Article ID:
e220357
Online Publication Date:
02 Jun 2023
Copyright:
© the author(s) 2023
Restricted access
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Clinical management of gastroenteropancreatic neuroendocrine neoplasms remains challenging. We recently introduced the FMS-like tyrosine kinase 3 ligand (FLT3LG) as a possible biomarker for a proinflammatory tumor microenvironment. Here, we put a spotlight on the quantitative assessment of classical dendritic cells (cDC) and T cells in the context of FLT3LG mRNA levels in a retrospective study on neuroendocrine tumor (NET) G2/G3 and neuroendocrine carcinoma (NEC) of pancreatic and gastric origin. The abundance of cDC and T cells and their relevant subpopulations were determined by immunofluorescent staining and correlated with FLT3LG mRNA levels as well as clinical outcomes. Immune cell counts attested to highly variable infiltration densities. Samples with the presence of cDC or high numbers of T cells exhibited increased FLT3LG expression. Abundance of cDC, defined as HLA-DR+CD11c+ cells with CLEC9a (cDC1) or CD1c (cDC2), as well as T cells correlated with FLT3LG mRNA levels and predicted disease-specific survival. Combining FLT3LG and T cell counts further improved this prediction. Therefore, tumor-infiltrating cDC and T cells are prognostic markers in NET G2/G3 or NEC and FLT3LG mRNA may serve as a simple-to-use biomarker for a quantitative estimate of their abundance, mandating prospective evaluation in the context of immune-targeted therapies.

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Print ISSN:
1351-0088
Online ISSN:
1479-6821
Copyright:
© the author(s) 2023
Article ID:
e220357
Received Date:
30 Mar 2023
Accepted Date:
02 May 2023
Print Publication Date:
01 Jul 2023
Online Publication Date:
02 Jun 2023
Keywords:
neuroendocrine neoplasm; neuroendocrine tumor; GEP-NEN; Flt3L; biomarker; tumor immune microenvironment; cDC1; T cells; CTL; immunotherapy

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