Work

ZBTB18 regulates cytokine expression and affects microglia/macrophage recruitment and commitment in glioblastoma

Year: 2024

Type: article

Abstract: Glioma associated macrophages/microglia (GAMs) play an important role in glioblastoma (GBM) progression, due to their massive recruitment to the tumor site and polarization to a tumor promoting phenotype. GAMs secrete a variety of cytokines, which facilitate tumor cell growth and invasion, and prevent other immune cells from mounting an immune response against the tumor. Here, we demonstrate that zinc finger and BTB containing domain 18 (ZBTB18), a transcriptional repressor with tumor suppressive function in glioblastoma, impairs the production of key cytokines, which function as chemoattractant for GAMs. Consistently, we observe a reduced migration of GAMs when ZBTB18 is expressed by glioblastoma cells, both in cell culture and in vivo experiments. Moreover, RNA sequencing analysis shows that the presence of ZBTB18 in glioblastoma cells alters the commitment of conditioned microglia, suggesting the loss of the immune-suppressive phenotype and the acquisition of pro-inflammatory features. Thus, therapeutic approaches to increase ZBTB18 expression in GBM cells could represent an effective adjuvant to immune therapy in GBM.

Source: Communications Biology

DOI: 10.1038/s42003-024-07144-y

Authors: Roberto Ferrarese, Kevin Joseph, Geoffroy Andrieux, Ira Verena Haase, Francesca Zanon, Eva Kling, Annalisa Izzo, Eyleen Corrales, Marius Schwabenland, Marco Prinz, Vidhya Madapusi Ravi, Melanie Boerries, Dieter Henrik Heiland, Maria Stella Carro

Institutions: University of Insubria, University of Freiburg, University Medical Center Freiburg

Language: English

Topic: Immune cells in cancer

Subfield: Immunology

Field: Immunology and Microbiology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,890

Funders: Deutsche Forschungsgemeinschaft, Bundesministerium für Bildung und Forschung, Albert-Ludwigs-Universität Freiburg, Deutsche Krebshilfe, Medizinische Fakultät der Albert-Ludwigs-Universität Freiburg

Awards: G1160281027, G1605809255, G1733652078, G2549159948, G2837854789, Zellsortiersystem, IMMPACT: Aufdecken gemeinsamer Prinzipien immunvermittelter Erkrankungen: von der Grundlagenwissenschaft zu neuen Therapien, G3256625789, PM4Onco - Medizininformatik-Use Case 'Personalisierte Medizin für die Onkologie' - Teilvorhaben: Koordination, Integration Krebsregisterdaten, Patient Journey, Kerndatensätze, Bioinformatik-/Dateninfrastrukturen, Erweiterte Analytik und Roll-Out: UK Freiburg, MIRACUM - Medizininformatik-Konsortium - Beitrag Universität Freiburg, G3544412130, SFB 1479: Onkogengetriebener Immun Escape (OncoEscape), SFB 1453: Nephrogenetik (NephGen), G449570878, SFB 1160: Immunpathologie aufgrund eingeschränkter Immunreaktionen (IMPATH), G4854266585, TRR 167: Entwicklung, Funktion und Potential von myeloiden Zellen im zentralen Nervensystem (NeuroMac), G5677642423, G5931083012, G6000535164, G6952166915, G735672719, G7399536025, G8694059555

OpenAlex ID: W4404172657

FWCI: 0.683

Cites: 69

Cited by: 5

Related to: 10