Medizinische Universität Graz - Research portal
Selected Publication:
SHR Neuro Cancer Cardio Lipid Metab Microb
Agrawal, D; Cisarova, K; Vosberg, S; Allmendinger, F; Munkhbaatar, E; Dandachi, N; Fernandez, Hernandez, FJ; Tonietto, M; Jäger, V; Anton, M; Keller, EC; Jesinghaus, M; Meinhardt, AL; Haefner, V; Stoeger, T; Steiger, K; McGranahan, N; Dengler, MA; Wahida, A; Jost, PJ.
Aberrant methylation limits antitumoral inflammation in lung adenocarcinoma by restricting RIPK3 expression.
Sci Adv. 2026; 12(4):eadz9227
Doi: 10.1126/sciadv.adz9227
PubMed
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- Leading authors Med Uni Graz
- Jost Philipp
- Vizar Cisarova Katarina
- Co-authors Med Uni Graz
- Dandachi Nadia
- Dengler Michael
- Fernandez Hernandez Francisco Jose
- Jäger Vanessa
- Tonietto Marta
- Vosberg Sebastian
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- Abstract:
- Evasion of programmed cell death is a critical hallmark of cancer. However, the contribution of inflammatory forms of cell death in lung carcinogenesis and their effects on the composition of the tumor-immune microenvironment remain unclear. Our multi-omics analyses of samples from patients with primary lung adenocarcinoma revealed that necrosome signaling is repressed because of reduced expression of receptor-interacting protein kinase 3 (RIPK3). Distinct methylation signatures, both in the RIPK3 promoter and nonpromoter regions, correlated with lower transcription levels of RIPK3. This resulted in limited expression of inflammatory genes, advanced histologic features, reduced immune cell invasion, and decreased patient survival. Mechanistically, we confirmed the tumor-suppressive role of necrosome signaling through the genetic deletion of Ripk3 in two independent, clinically relevant mouse models of lung adenocarcinoma. Functionally, RIPK3 shaped a diverse immune environment by promoting the invasion of innate and adaptive immune cells in patient samples and experimental mice. Thus, RIPK3-mediated inflammatory signaling enhances a diverse immune microenvironment and hinders progression in lung adenocarcinoma.
- Find related publications in this database (using NLM MeSH Indexing)
- Receptor-Interacting Protein Serine-Threonine Kinases - genetics, metabolism
- Adenocarcinoma of Lung - genetics, pathology, metabolism, immunology
- Animals - administration & dosage
- Humans - administration & dosage
- Mice - administration & dosage
- Lung Neoplasms - genetics, pathology, metabolism, immunology
- Inflammation - genetics, pathology, metabolism
- DNA Methylation - administration & dosage
- Tumor Microenvironment - genetics, immunology
- Gene Expression Regulation, Neoplastic - administration & dosage
- Signal Transduction - administration & dosage
- Disease Models, Animal - administration & dosage
- Cell Line, Tumor - administration & dosage
- Promoter Regions, Genetic - administration & dosage