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| Status |
Public on Mar 01, 2021 |
| Title |
RNA sequencing of blood-brain barrier (BBB) microvessels from mice with orthotopic GBM showing the benefit of triple therapy combining anti-immune checkpoint therapy with dual-anti angiogenic therapy. |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Glioblastoma multiforme (GBM) is a non T cell-inflamed cancer characterized by an immunosuppressive microenvironment that impedes dendritic cell maturation and T cell cytotoxicity. The alleviation of immunosuppression might be a prerequisite for succesful immune checkpoint therapy in GBM. We here combine anti-angiogenic and immune checkpoint therapy and demonstrate improved therapeutic efficacy in syngeneic, orthotopic GBM models. We observed that blockade of vascular endothelial growth factor (VEGF), Angiopoietin-2 (Ang-2) and programmed cell death protein-1 (PD-1) significantly extended survival compared to vascular targeting alone. In the GBM microenvironment, triple therapy increased the numbers of cytotoxic T-lymphocytes that inversely correlated with myeloid-derived suppressor and regulatory T cells. Furthermore, transcriptomic analysis of GBM microvessels indicates a global vascular normalization that was highest after triple therapy. Our results propose a rationale to overcome limitations of VEGF monotherapy by integrating the synergistic effects of VEGF/Ang-2 and PD-1 blockade to reinforce anti-tumor immunity through a normalized vasculature.
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| Overall design |
Brain microvessels were isolated from treated and untreated adult WT BL6/57 mice from tumor bearing brain region at 21 days post transplation followed by RNA sequecning. Three biological replicates were included for each group pooling 3 mice for each set. Contra-lateral brain region within each group and sham operated mice served as controls.
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| Contributor(s) |
Kavi D, Yvonne R, Stefan G |
| Citation(s) |
31597643 |
| |
| Submission date |
Apr 25, 2019 |
| Last update date |
May 31, 2021 |
| Contact name |
Stefan Günther |
| E-mail(s) |
stefan.guenther@mpi-bn.mpg.de
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| Organization name |
MPI for heart and lung research
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| Street address |
ludwigtr. 43
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| City |
bad nauheim |
| ZIP/Postal code |
61231 |
| Country |
Germany |
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| Platforms (1) |
| GPL19057 |
Illumina NextSeq 500 (Mus musculus) |
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| Samples (15)
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| Relations |
| BioProject |
PRJNA535500 |
| SRA |
SRP193869 |
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