Single-cell landscape of the tumour immune microenvironment in human gynaecologic malignancies

The immune microenvironment of the three most common gynaecological malignancies-tubo-ovarian cancer, endometrial cancer and cervical cancer-has not been systematically studied, limiting clinical application.

This study analyses 272 389 CD45+ immune cells by integrating publicly available single-cell RNA sequencing (scRNA-seq) data from 111 tumour and non-malignant tissue samples. We identified distinct subsets within immune cells: 11 for monocytes/macrophages, six for CD4 T cells, eight for CD8 T cells and five for B cells, detailing their distribution, prevalence and distinct functions.

A pro-angiogenic macrophage subset linked to NF-κB signalling was associated with worse clinical outcomes and an interferon-primed macrophage subset correlated with improved survival by recruiting T cells through CXCL9/10/11 secretion, as confirmed by multi-colour immunohistochemistry. T cells exhibited dynamic roles in tubo-ovarian cancer, with CD8 Tex cells contributing to immune dysfunction and poor prognosis, while CD8 Trm cells in early-stage tumours supported immune surveillance. Additionally, we identified co-stimulatory and co-inhibitory receptor interactions and classified distinct B cell subsets with varying prognostic implications.

This comprehensive analysis of the tumour immune microenvironment in gynaecological malignancies provides new insights into immune cell composition and function offering potential for optimising immunotherapies and improving clinical outcomes in these cancers.