EGFL7 promotes immune evasion in glioma through its interaction with integrin β₂ Article Swipe

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Sukrit Mahajan , Patrick M. Abe , Fanny Ehret , Carina Fabian , Nora Heinig , Kathrin Barth , Marc Gentzel , Rajinder K. Gupta , Julieta Aprea , Peter C. Warnke , Beatrice Wasser , Stephan Grabbe , Marc Schmitz , Andreas Dahl , Frauke Zipp , Ulrike Schumann , Mirko H. H. Schmidt ·

YOU? · · 2025 · Open Access · · DOI: https://doi.org/10.1101/2025.07.28.667281

Glioblastoma is the most aggressive form of malignant brain cancer, characterized by an immunosuppressive microenvironment and extensive angiogenesis. Epidermal growth factor-like protein 7 (EGFL7), a secreted pro-angiogenic factor that is highly expressed in the glioblastoma microenvironment (GME), has been implicated in immune evasion by other solid tumors, but its role in glioblastoma immune regulation remains unclear. Here, we studied the impact of EGFL7 in shaping the immune landscape in glioblastoma and identified underlying mechanisms. Single-cell transcriptomic profiling of immune cells from glioblastoma models revealed that EGFL7 promotes an immunosuppressive GME, characterized by increased infiltration of pro-tumorigenic macrophages and enhanced T cell exhaustion. Mechanistically, EGFL7 interacts with integrin β2 (ITGB2) on immune cells to mediate these effects. Genetic perturbation of the EGFL7-ITGB2 axis attenuated immunosuppression and significantly prolonged the survival of glioblastoma-bearing mice. In conclusion, our study provides unequivocal evidence that the EGFL7-ITGB2 axis acts as a critical mediator of immunosuppression in glioblastoma and represents a potential therapeutic target for reprogramming the GME to prevent immune evasion in glioblastoma.

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Evasion (ethics) Glioma Immune system Integrin Cancer research Immunology Chemistry Biology Receptor Biochemistry

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Type: preprint
Language: en
Landing Page: https://doi.org/10.1101/2025.07.28.667281
PDF: https://www.biorxiv.org/content/biorxiv/early/2025/07/31/2025.07.28.667281.full.pdf
OA Status: green
References: 57
Related Works: 10
OpenAlex ID: https://openalex.org/W4412792117

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DOI: https://doi.org/10.1101/2025.07.28.667281

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Title: EGFL7 promotes immune evasion in glioma through its interaction with integrin β₂

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Type: preprint

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Language: en

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Publication year: 2025

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Publication date: 2025-07-31

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Authors: Sukrit Mahajan, Patrick M. Abe, Fanny Ehret, Carina Fabian, Nora Heinig, Kathrin Barth, Marc Gentzel, Rajinder K. Gupta, Julieta Aprea, Peter C. Warnke, Beatrice Wasser, Stephan Grabbe, Marc Schmitz, Andreas Dahl, Frauke Zipp, Ulrike Schumann, Mirko H. H. Schmidt

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Landing page: https://doi.org/10.1101/2025.07.28.667281

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PDF URL: https://www.biorxiv.org/content/biorxiv/early/2025/07/31/2025.07.28.667281.full.pdf

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OA URL: https://www.biorxiv.org/content/biorxiv/early/2025/07/31/2025.07.28.667281.full.pdf

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Concepts: Evasion (ethics), Glioma, Immune system, Integrin, Cancer research, Immunology, Chemistry, Biology, Receptor, Biochemistry

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EGFL7 promotes immune evasion in glioma through its interaction with integrin β2 Article Swipe

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EGFL7 promotes immune evasion in glioma through its interaction with integrin β₂ Article Swipe