GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery

Casper H.J. van Eijck*, Francisco X. Real, Núria Malats, the Dutch Pancreatic Cancer Group (DPCG), Disha Vadgama, Thierry P.P. van den Bosch, Michail Doukas, Casper H.J. van Eijck, Dana A.M. Mustafa*

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

This study underscores GATA6’s role in distinguishing classical and basal-like pancreatic ductal adenocarcinoma (PDAC) phenotypes. Retrospective studies associate GATA6 immunohistochemistry (IHC) expression with survival outcomes, warranting prospective validation. In a prospective treatment-naive cohort of patients with resected PDAC, GATA6 IHC proves a prognostic discriminator, associating high GATA6 expression with extended survival and the classical PDAC phenotype. However, GATA6’s prognostic significance is numerically lower after gemcitabine-based neoadjuvant chemoradiotherapy compared to its significance in patients treated with upfront surgery. Furthermore, GATA6 is implicated in immunomodulation, although a comprehensive investigation of its immunological role is lacking. Treatment-naive PDAC tumors with varying GATA6 expression yield distinct immunological landscapes. Tumors highly expressing GATA6 show reduced infiltration of immunosuppressive regulatory T cells and M2 macrophages but increased infiltration of immune-stimulating, antigen-presenting, and activated T cells. Our findings caution against solely relying on GATA6 for molecular subtyping in clinical trials and open avenues for exploring immune-based combination therapies.

Original languageEnglish
Article number101557
JournalCell Reports Medicine
Volume5
Issue number5
DOIs
Publication statusPublished - 21 May 2024

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Publisher Copyright: © 2024 The Author(s)

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