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| Status |
Public on Oct 11, 2024 |
| Title |
Immunotherapies that repolarize macrophages and regulatory T cells enhance the effect of chemotherapy in high-grade serous ovarian cancer (Mouse) |
| Organism |
Mus musculus |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
We conducted single-cell RNA sequencing (scRNAseq) of tumor-infiltrating immune cells in high-grade serous ovarian cancer (HGSOC) omental biopsies to identify potential targets that could enhance response to neo-adjuvant chemotherapy (NACT). Analysis of 64,097 cells identified NACT-induced overexpression of stabilin-1 (clever-1) on macrophages and FOXP3 in Tregs and these were validated at the protein level. STAB1 inhibition in vitro induced anti-tumor macrophages. FOXP3 anti-sense oligonucleotide (FOXP3-ASO), repolarised Tregs to an effector T cell phenotype.
ScRNAseq on 69,781 cells from an HGSOC syngeneic mouse model recapitulated the patients’ data. Combining chemotherapy with anti-stabilin1 antibody and/or Foxp3-ASO significantly increased survival of mice with established peritoneal disease in two HGSOC syngeneic models and progression-free survival in a third model. Long-term survivors (300 days+) were resistant to tumor rechallenge. Anti-stabilin1 antibody enriched the tumors with CXCL9+ macrophages and Foxp3-ASO increased TBET cell infiltration. Our results suggest targeting these molecules may improve chemotherapy response in patients.
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| Overall design |
Single cell RNA sequencing on whole omental tumours from HGS2 mouse model. Tumours were harvested from three control mice and 3 mice one week after the third dose of carboplatin and paclitaxel.
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| Web link |
http://DOI: 10.1038/s41467-024-54295-x
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| Contributor(s) |
Elorbany S, Berlato C, Carnevalli LS, Maniati E, Wang J, Barry ST, Manchanda R, Kzhyshkowska J, Balkwill F |
| Citation(s) |
39578450 |
| |
| Submission date |
Feb 02, 2023 |
| Last update date |
Jan 18, 2025 |
| Contact name |
Samar Elorbany |
| E-mail(s) |
s.elorbany@qmul.ac.uk
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| Organization name |
Queen Mary University of London
|
| Department |
Tumour Microenvironment
|
| Street address |
Barbican
|
| City |
London |
| ZIP/Postal code |
EC1M 6BQ |
| Country |
United Kingdom |
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| Platforms (1) |
| GPL24247 |
Illumina NovaSeq 6000 (Mus musculus) |
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| Samples (18)
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| Relations |
| BioProject |
PRJNA930760 |
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