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Breaking the feed forward inflammatory cytokine loop in the tumor microenvironment of PDGFB-driven glioblastomas
C. Ryan Miller, Anita B. Hjelmeland
C. Ryan Miller, Anita B. Hjelmeland
Published November 15, 2023
Citation Information: J Clin Invest. 2023;133(22):e175127. https://doi.org/10.1172/JCI175127.
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Commentary

Breaking the feed forward inflammatory cytokine loop in the tumor microenvironment of PDGFB-driven glioblastomas

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Abstract

Glioblastoma (GBM) tumor-associated macrophages (TAMs) provide a major immune cell population contributing to growth and immunosuppression via the production of proinflammatory factors, including IL-1. In this issue of the JCI, Chen, Giotti, and colleagues investigated loss of ll1b in the immune tumor microenvironment (TME) in GBM models driven by PDGFB expression and Nf1 knockdown. Survival was only improved in PDGFB-driven GBM models, suggesting that tumor cell genotype influenced the immune TME. IL-1β in the TME increased PDGFB-driven GBM growth by increasing tumor-derived NF-κB, expression of monocyte chemoattractants, and increased infiltration of bone marrow–derived myeloid cells (BMDMs). In contrast, no requirement for IL-1β was evident in Nf1-silenced tumors due to high basal levels of NF-κB and monocyte chemoattractants and increased infiltration of BMDM and TAMs. Notably, treatment of mice bearing PDGFB-driven GBM with anti–IL-1β or an IL1R1 antagonist extended survival. These findings suggest that effective clinical immunotherapy may require differential targeting strategies.

Authors

C. Ryan Miller, Anita B. Hjelmeland

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