Titre
GSDMD is associated with survival in human breast cancer but does not impact anti-tumor immunity in a mouse breast cancer model.
Type
article
Institution
UNIL/CHUV/Unisanté + institutions partenaires
Périodique
Auteur(s)
Boersma, B.
Auteure/Auteur
Puddinu, V.
Auteure/Auteur
Huard, A.
Auteure/Auteur
Fauteux-Daniel, S.
Auteure/Auteur
Wirapati, P.
Auteure/Auteur
Guedri, S.
Auteure/Auteur
Tille, J.C.
Auteure/Auteur
McKee, T.
Auteure/Auteur
Pittet, M.
Auteure/Auteur
Palmer, G.
Auteure/Auteur
Bourquin, C.
Auteure/Auteur
Liens vers les personnes
Liens vers les unités
ISSN
1664-3224
Statut éditorial
Publié
Date de publication
2024
Volume
15
Première page
1396777
Peer-reviewed
Oui
Langue
anglais
Notes
Publication types: Journal Article
Publication Status: epublish
Publication Status: epublish
Résumé
Inflammation plays a pivotal role in cancer development, with chronic inflammation promoting tumor progression and treatment resistance, whereas acute inflammatory responses contribute to protective anti-tumor immunity. Gasdermin D (GSDMD) mediates the release of pro-inflammatory cytokines such as IL-1β. While the release of IL-1β is directly linked to the progression of several types of cancers, the role of GSDMD in cancer is less clear. In this study, we show that GSDMD expression is upregulated in human breast, kidney, liver, and prostate cancer. Higher GSDMD expression correlated with increased survival in primary breast invasive carcinoma (BRCA), but not in liver hepatocellular carcinoma (LIHC). In BRCA, but not in LIHC, high GSDMD expression correlated with a myeloid cell signature associated with improved prognosis. To further investigate the role of GSDMD in anticancer immunity, we induced breast cancer and hepatoma tumors in GSDMD-deficient mice. Contrary to our expectations, GSDMD deficiency had no effect on tumor growth, immune cell infiltration, or cytokine expression in the tumor microenvironment, except for Cxcl10 upregulation in hepatoma tumors. In vitro and in vivo innate immune activation with TLR ligands, that prime inflammatory responses, revealed no significant difference between GSDMD-deficient and wild-type mice. These results suggest that the impact of GSDMD on anticancer immunity is dependent on the tumor type. They underscore the complex role of inflammatory pathways in cancer, emphasizing the need for further exploration into the multifaceted effects of GSDMD in various tumor microenvironments. As several pharmacological modulators of GSDMD are available, this may lead to novel strategies for combination therapy in cancer.
Sujets
PID Serval
serval:BIB_FA09590DDCEE
PMID
Open Access
Oui
Date de création
2024-09-09T12:50:46.323Z
Date de création dans IRIS
2025-05-21T07:16:43Z
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Nom
39224600_BIB_FA09590DDCEE.pdf
Version du manuscrit
published
Licence
https://creativecommons.org/licenses/by/4.0
Taille
3.07 MB
Format
Adobe PDF
PID Serval
serval:BIB_FA09590DDCEE.P001
URN
urn:nbn:ch:serval-BIB_FA09590DDCEE3
Somme de contrôle
(MD5):01ac6a11c81f86d9905447e02b9c5d00