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| Item Type: | Article |
|---|---|
| Title: | Sensitization of glioblastoma tumor micro-environment to chemo- and immunotherapy by Galectin-1 intranasal knock-down strategy |
| Creators: |
Van Woensel, M., Mathivet, T., Wauthoz, N., Rosière, R., Garg, A.D., Agostinis, P., Mathieu, V., Kiss, R., Lefranc, F., Boon, L., Belmans, J., Van Gool, S.W., Gerhardt, H.  ORCID: https://orcid.org/0000-0002-3030-0384, Amighi, K. and De Vleeschouwer, S.
|
| Abstract: | In this study, we evaluated the consequences of reducing Galectin-1 (Gal-1) in the tumor micro-environment (TME) of glioblastoma multiforme (GBM), via nose-to-brain transport. Gal-1 is overexpressed in GBM and drives chemo- and immunotherapy resistance. To promote nose-to-brain transport, we designed siRNA targeting Gal-1 (siGal-1) loaded chitosan nanoparticles that silence Gal-1 in the TME. Intranasal siGal-1 delivery induces a remarkable switch in the TME composition, with reduced myeloid suppressor cells and regulatory T cells, and increased CD4+ and CD8+ T cells. Gal-1 knock-down reduces macrophages' polarization switch from M1 (pro-inflammatory) to M2 (anti-inflammatory) during GBM progression. These changes are accompanied by normalization of the tumor vasculature and increased survival for tumor bearing mice. The combination of siGal-1 treatment with temozolomide or immunotherapy (dendritic cell vaccination and PD-1 blocking) displays synergistic effects, increasing the survival of tumor bearing mice. Moreover, we could confirm the role of Gal-1 on lymphocytes in GBM patients by matching the Gal-1 expression and their T cell signatures. These findings indicate that intranasal siGal-1 nanoparticle delivery could be a valuable adjuvant treatment to increase the efficiency of immune-checkpoint blockade and chemotherapy. |
| Keywords: | Intranasal, Administration, Animal, Disease Models, Drug Therapy, Galectin, Gene Knockdown Techniques, Glioblastoma, Immunotherapy, Small Interfering, RNA, Treatment Outcome, Tumor Microenvironment, Animals, Mice |
| Source: | Scientific Reports |
| ISSN: | 2045-2322 |
| Publisher: | Nature Publishing Group |
| Volume: | 7 |
| Number: | 1 |
| Page Range: | 1217 |
| Date: | 27 April 2017 |
| Official Publication: | https://doi.org/10.1038/s41598-017-01279-1 |
| PubMed: | View item in PubMed |
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