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| Item Type: | Article |
|---|---|
| Title: | Single-cell profiling and zebrafish avatars reveal LGALS1 as immunomodulating target in glioblastoma |
| Creators: |
Finotto, L.  ORCID: https://orcid.org/0000-0002-4695-9343, Cole, B. ORCID: https://orcid.org/0000-0001-5899-5598, Giese, W. ORCID: https://orcid.org/0000-0003-0872-0929, Baumann, E. ORCID: https://orcid.org/0000-0002-7804-4885, Claeys, A., Vanmechelen, M. ORCID: https://orcid.org/0000-0002-8342-3150, Decraene, B. ORCID: https://orcid.org/0000-0002-2523-452X, Derweduwe, M. ORCID: https://orcid.org/0000-0002-4960-4847, Dubroja Lakic, N., Shankar, G., Nagathihalli Kantharaju, M., Albrecht, J.P. ORCID: https://orcid.org/0000-0002-3792-9695, Geudens, I. ORCID: https://orcid.org/0000-0003-3297-4208, Stanchi, F. ORCID: https://orcid.org/0000-0003-3393-2472, Ligon, K.L. ORCID: https://orcid.org/0000-0002-7733-600X, Boeckx, B. ORCID: https://orcid.org/0000-0002-0296-6680, Lambrechts, D. ORCID: https://orcid.org/0000-0002-3429-302X, Harrington, K. ORCID: https://orcid.org/0000-0002-7237-1973, Van Den Bosch, L. ORCID: https://orcid.org/0000-0003-0104-4067, De Vleeschouwer, S. ORCID: https://orcid.org/0000-0002-9576-9917, De Smet, F. ORCID: https://orcid.org/0000-0002-6669-3335 and Gerhardt, H. ORCID: https://orcid.org/0000-0002-3030-0384
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| Abstract: | Glioblastoma (GBM) remains the most malignant primary brain tumor, with a median survival rarely exceeding 2 years. Tumor heterogeneity and an immunosuppressive microenvironment are key factors contributing to the poor response rates of current therapeutic approaches. GBM-associated macrophages (GAMs) often exhibit immunosuppressive features that promote tumor progression. However, their dynamic interactions with GBM tumor cells remain poorly understood. Here, we used patient-derived GBM stem cell cultures and combined single-cell RNA sequencing of GAM-GBM co-cultures and real-time in vivo monitoring of GAM-GBM interactions in orthotopic zebrafish xenograft models to provide insight into the cellular, molecular, and spatial heterogeneity. Our analyses revealed substantial heterogeneity across GBM patients in GBM-induced GAM polarization and the ability to attract and activate GAMs—features that correlated with patient survival. Differential gene expression analysis, immunohistochemistry on original tumor samples, and knock-out experiments in zebrafish subsequently identified LGALS1 as a primary regulator of immunosuppression. Overall, our work highlights that GAM-GBM interactions can be studied in a clinically relevant way using co-cultures and avatar models, while offering new opportunities to identify promising immune-modulating targets. |
| Keywords: | Glioblastoma, LGALS1, Macrophages, scRNA-seq, Zebrafish Avatars, Animals, Zebrafish |
| Source: | EMBO Molecular Medicine |
| ISSN: | 1757-4676 |
| Publisher: | EMBO Press / Wiley |
| Volume: | 15 |
| Number: | 11 |
| Page Range: | e18144 |
| Date: | 8 November 2023 |
| Official Publication: | https://doi.org/10.15252/emmm.202318144 |
| PubMed: | View item in PubMed |
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