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Citations to this article

Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma
Yang Liu, … , Amy B. Heimberger, Peiwen Chen
Yang Liu, … , Amy B. Heimberger, Peiwen Chen
Published October 1, 2024
Citation Information: J Clin Invest. 2024;134(22):e178628. https://doi.org/10.1172/JCI178628.
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Research Article Oncology Article has an altmetric score of 8

Dual targeting macrophages and microglia is a therapeutic vulnerability in models of PTEN-deficient glioblastoma

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Abstract

Tumor-associated macrophages and microglia (TAMs) are critical for tumor progression and therapy resistance in glioblastoma (GBM), a type of incurable brain cancer. We previously identified lysyl oxidase (LOX) and olfactomedin like-3 (OLFML3) as essential macrophage and microglia chemokines, respectively, in GBM. Here, single-cell transcriptomics and multiplex sequential immunofluorescence followed by functional studies demonstrate that macrophages negatively correlate with microglia in the GBM tumor microenvironment. LOX inhibition in PTEN-deficient GBM cells upregulates OLFML3 expression via the NF-κB-PATZ1 signaling pathway, inducing a compensatory increase of microglia infiltration. Dual targeting macrophages and microglia via inhibition of LOX and the CLOCK-OLFML3 axis generates potent antitumor effects and offers a complete tumor regression in more than 60% of animals when combined with anti-PD1 therapy in PTEN-deficient GBM mouse models. Thus, our findings provide a translational triple therapeutic strategy for this lethal disease.

Authors

Yang Liu, Junyan Wu, Hinda Najem, Yiyun Lin, Lizhi Pang, Fatima Khan, Fei Zhou, Heba Ali, Amy B. Heimberger, Peiwen Chen

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Total citations by year

Year: 2025 Total
Citations: 3 3
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Citations to this article (3)

Title and authors Publication Year
The Impact of Metabolic Rewiring in Glioblastoma: The Immune Landscape and Therapeutic Strategies
Vijayanathan Y, Ho IA
International Journal of Molecular Sciences 2025
Microenvironmental Drivers of Glioma Progression
Jang HJ, Park JW
International Journal of Molecular Sciences 2025
Epigenetic reprogramming and antitumor immune responses in gliomas: a systematic review.
Riyas Mohamed FR, Yaqinuddin A
Medical oncology (Northwood, London, England) 2025

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Copyright © 2025 American Society for Clinical Investigation
ISSN: 0021-9738 (print), 1558-8238 (online)

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