Immunotherapy that improves response to chemotherapy in high-grade serous ovarian cancer
Single-cell RNA sequencing (scRNAseq) of tumour-infiltrating immune cells in high-grade serous ovarian cancer (HGSOC) omental biopsies reveals potential targets that could enhance response to neo-adjuvant chemotherapy (NACT). Analysis of 64,097 cells identifies NACT-induced overexpression of stabili...
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| Hauptverfasser: | , , , , , , , , |
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| Dokumenttyp: | Article (Journal) |
| Sprache: | Englisch |
| Veröffentlicht: |
22 November 2024
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| In: |
Nature Communications
Year: 2024, Jahrgang: 15, Pages: 1-20 |
| ISSN: | 2041-1723 |
| DOI: | 10.1038/s41467-024-54295-x |
| Online-Zugang: | Verlag, lizenzpflichtig, Volltext: https://doi.org/10.1038/s41467-024-54295-x Verlag, lizenzpflichtig, Volltext: https://www.nature.com/articles/s41467-024-54295-x 
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| Verfasserangaben: | Samar Elorbany, Chiara Berlato, Larissa S. Carnevalli, Eleni Maniati, Simon T. Barry, Jun Wang, Ranjit Manchanda, Julia Kzhyshkowska & Frances Balkwill |
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| 520 | |a Single-cell RNA sequencing (scRNAseq) of tumour-infiltrating immune cells in high-grade serous ovarian cancer (HGSOC) omental biopsies reveals potential targets that could enhance response to neo-adjuvant chemotherapy (NACT). Analysis of 64,097 cells identifies NACT-induced overexpression of stabilin-1 (clever-1) on macrophages and FOXP3 in Tregs that is confirmed at the protein level. STAB1 inhibition in vitro induces anti-tumour macrophages. FOXP3 anti-sense oligonucleotide (FOXP3-ASO), repolarises Tregs to an effector T cell phenotype. ScRNAseq on 69,781 cells from an HGSOC syngeneic mouse model recapitulates the patients’ data. Combining chemotherapy with anti-stabilin1 antibody and/or Foxp3-ASO significantly increases 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 + ) are resistant to tumour rechallenge. Anti-stabilin1 antibody enriches the tumours with CXCL9+ macrophages and Foxp3-ASO increases TBET cell infiltration. Our results suggest that targeting these molecules in immune cells may improve chemotherapy response in patients. | ||
| 650 | 4 | |a Ovarian cancer | |
| 650 | 4 | |a Translational research | |
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