Publications

Authors:

Peng, Juanfei; Yang, Jiajin; Antonopoulou, Georgia; Fang, Rui; Adhikari, Bikash; Vogt, Markus; Wolf, Elmar; Sun, Chong; Du, Shangce; Godfrey, Laura; Gupta, Aayush; Trajkovic-Arsic, Marija; Teichmann, Nicole; Grünwald, Barbara T; Krebs, Niklas; Steiger, Katja; Mogler, Carolin; Althoff, Kristina; Wang, Xin; Giglio, Giovanni; Liffers, Sven-Thorsten; Savvatakis, Konstantinos; Braren, Rickmer; Lawlor, Rita T; Scarpa, Aldo; Behrens, Diana; Lang, Karl S; Cheung, Phyllis F; Siveke, Jens T

Title:

Combined targeted and epigenetic-based therapy enhances antitumor immunity by stabilizing GATA6-dependent MHCI expression in pancreatic ductal adenocarcinoma

Year:

2026

Type of item:

Articolo in Rivista

Tipologia ANVUR:

Articolo su rivista

Language:

Inglese

Format:

Elettronico

Referee:

No

Name of journal:

NATURE COMMUNICATIONS

ISSN of journal:

2041-1723

N° Volume:

17

Number or Folder:

1

Page numbers:

1-21

Keyword:

Animals; Carcinoma, Pancreatic Ductal; CD8-Positive T-Lymphocytes; Cell Line, Tumor; Epigenesis, Genetic; Epithelial-Mesenchymal Transition; Female; GATA6 Transcription Factor; Gene Expression Regulation, Neoplastic; Histone Deacetylase Inhibitors; Humans; Mice; Mice, Inbred C57BL; Pancreatic Neoplasms; Protein Kinase Inhibitors

Short description of contents:

: GATA6 promotes epithelial phenotypes and limits epithelial-to-mesenchymal (EMT) transition in pancreatic ductal adenocarcinoma (PDAC). Here we show that GATA6 defines a tumor cell state that induces MHCI expression and anti-tumor cytotoxicity upon therapy. In human PDAC, GATA6 expression correlates with immune cell infiltration, and spatial analysis reveals interaction between GATA6+ tumor cells and CD8+ T cells. In murine PDAC, MEK inhibition (MEKi) enriches antigenicity-related gene sets in GATA6high cells, while GATA6 knockout or degradation impairs MEKi-induced MHCI upregulation. High-GATA6 tumors respond to MEKi with increased MHCI, enhancing T-cell cytotoxicity, whereas GATA6 loss abolishes this effect. Treatment-induced EMT reduces GATA6+ populations and MHCI expression, which is restored by combining MEKi with HDAC inhibitors, enhancing GATA6+ tumor cells, MHCI, CD8+ T cell infiltration, tumor suppression, and survival. These findings suggest that therapeutic strategies promoting a GATA6-driven tumor cell state improve immune recognition of PDAC cells and potentiate anti-tumor cytotoxic effects.

Note:

The online version contains supplementary material available at https://doi.org/10.1038/s41467-026-69013-y

Product ID:

149709

Handle IRIS:

11562/1182409

Last Modified:

February 22, 2026

Bibliographic citation:

Peng, Juanfei; Yang, Jiajin; Antonopoulou, Georgia; Fang, Rui; Adhikari, Bikash; Vogt, Markus; Wolf, Elmar; Sun, Chong; Du, Shangce; Godfrey, Laura; Gupta, Aayush; Trajkovic-Arsic, Marija; Teichmann, Nicole; Grünwald, Barbara T; Krebs, Niklas; Steiger, Katja; Mogler, Carolin; Althoff, Kristina; Wang, Xin; Giglio, Giovanni; Liffers, Sven-Thorsten; Savvatakis, Konstantinos; Braren, Rickmer; Lawlor, Rita T; Scarpa, Aldo; Behrens, Diana; Lang, Karl S; Cheung, Phyllis F; Siveke, Jens T, Combined targeted and epigenetic-based therapy enhances antitumor immunity by stabilizing GATA6-dependent MHCI expression in pancreatic ductal adenocarcinoma «NATURE COMMUNICATIONS» , vol. 17 , n. 1 , 2026 , pp. 1-21

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