Objective:

To delineate cellular communication networks shaping immune dysfunction within HGSOC ascites, identify key regulatory signalling pathways, characterize the fibroblast–macrophage axis at single-cell resolution, and evaluate the therapeutic potential of IL-10 blockade.

Approach:

• Single-Cell RNA Sequencing: Analyzed single-cell RNA sequencing data from eight ascites samples of six HGSOC patients using Seurat for clustering and differential expression.
• Cell Communication Analysis: Utilized CellChat to infer ligand–receptor communication and sub-clustered to define iCAF, mCAF, and macrophage subtypes.
• Functional Pathway Assessment: Conducted GO/KEGG enrichment to assess functional pathways.
• Multiplex Immunofluorescence: Validated spatial interactions of IL10+ iCAF and IL10RA+ macrophages in patient tissues.
• Therapeutic Evaluation: Established an immune-humanized PDX mouse model to evaluate the therapeutic effect of IL-10 blockade.

Key Findings:

• Macrophages and cancer-associated fibroblasts are dominant cell populations in HGSOC ascites.
• IL-10–IL-10RA signalling is a prominent interaction pathway linking iCAFs with M2-like macrophages.
• iCAFs express elevated IL-10, while M2 macrophages show increased IL-10RA/IL-10RB expression and are associated with exhausted immune states.
• IL-10 blockade with MK-1966 significantly suppressed tumour growth and reduced M2 macrophage markers in PDX models.

Interpretation:

This study identifies an IL-10-dependent iCAF–M2 macrophage immunoregulatory circuit as a central mechanism driving immune suppression in HGSOC.

Conclusion:

Targeting the IL-10 pathway effectively reverses M2 polarization and suppresses tumour progression, highlighting IL-10 blockade as a promising therapeutic strategy in ovarian cancer.