Buchumschlag

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...

Ausführliche Beschreibung

Gespeichert in:
Bibliographische Detailangaben
Hauptverfasser: Elorbany, Samar (VerfasserIn) , Berlato, Chiara (VerfasserIn) , Carnevalli, Larissa S. (VerfasserIn) , Maniati, Eleni (VerfasserIn) , Barry, Simon T. (VerfasserIn) , Wang, Jun (VerfasserIn) , Manchanda, Ranjit (VerfasserIn) , Kzhyshkowska, Julia (VerfasserIn) , Balkwill, Frances (VerfasserIn)
Dokumenttyp: Article (Journal)
Sprache:Englisch
Veröffentlicht: 22 November 2024
In: Nature Communications
Year: 2024, Jahrgang: 15, Pages: 1-20
ISSN:2041-1723
DOI:10.1038/s41467-024-54295-x
Online-Zugang:lizenzpflichtig
lizenzpflichtig
Volltext
Verfasserangaben:Samar Elorbany, Chiara Berlato, Larissa S. Carnevalli, Eleni Maniati, Simon T. Barry, Jun Wang, Ranjit Manchanda, Julia Kzhyshkowska & Frances Balkwill
Beschreibung
Zusammenfassung: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.
Beschreibung:Gesehen am 28.04.2025
Beschreibung:Online Resource
ISSN:2041-1723
DOI:10.1038/s41467-024-54295-x

Ähnliche Einträge