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

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• dc.contributor.author van Eijck, Casper W. F.
• dc.contributor.author Real, Francisco X.
• dc.contributor.author Malats i Riera, Núria
• dc.contributor.author Vadgama, Disha
• dc.contributor.author van den Bosch, Thierry P. P.
• dc.contributor.author Doukas, Michail
• dc.contributor.author van Eijck, Casper H. J.
• dc.contributor.author Mustafa, Dana A. M.
• dc.contributor.author Dutch Pancreatic Cancer Group (DPCG)
• dc.date.accessioned 2024-06-11T06:13:30Z
• dc.date.available 2024-06-11T06:13:30Z
• dc.date.issued 2024
• dc.description.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.
• dc.description.sponsorship The laboratory of C.H.J.v.E. receives financial support from the Survival with Pancreatic Cancer Foundation (www.supportcasper.nl) (grant number OVIT17-06). The laboratory of F.X.R. receives financial support from Ministerio de Ciencia, Innovación y Universidades (grant number PID2020-119533GB-I00). The CNIO receives support from the Ministerio de Ciencia, Innovación y Universidades as a Centro de Excelencia Severo Ochoa (grant number SEV-2015-0510).
• dc.format.mimetype application/pdf
• dc.identifier.citation van Eijck CWF, Real FX, Malats N, Vadgama D, van den Bosch TPP, Doukas M, et al. GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery. Cell Rep Med. 2024 May 21;5(5):101557. DOI: 10.1016/j.xcrm.2024.101557
• dc.identifier.doi http://dx.doi.org/10.1016/j.xcrm.2024.101557
• dc.identifier.issn 2666-3791
• dc.identifier.uri http://hdl.handle.net/10230/60422
• dc.language.iso eng
• dc.publisher Elsevier
• dc.relation.ispartof Cell Rep Med. 2024 May 21;5(5):101557
• dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/PID2020-119533GB-I00
• dc.rights © 2024 The Author(s). Published by Elsevier Inc. This is an open access article under the CC BY license (http://creativecommons.org/licenses/by/4.0/).
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.rights.uri http://creativecommons.org/licenses/by/4.0/
• dc.subject.keyword GATA6
• dc.subject.keyword PDAC
• dc.subject.keyword Immune profiling
• dc.subject.keyword Pancreatic ductal adenocarcinoma
• dc.subject.keyword Randomized controlled trial
• dc.subject.keyword Tumor microenvironment
• dc.title GATA6 identifies an immune-enriched phenotype linked to favorable outcomes in patients with pancreatic cancer undergoing upfront surgery
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/publishedVersion