Immunotherapy that improves response to chemotherapy in high-grade serous ovarian cancer.

ABSTRACT: 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 s

SUBMITTER: Elorbany S 

PROVIDER: S-EPMC11584700 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature