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

## TL;DR

This study maps immune cells in gynaecological cancers, revealing how specific immune cell types affect cancer outcomes and treatment potential.

## Contribution

The study provides a detailed single-cell atlas of immune cell subsets and their functional roles in three major gynaecological cancers.

## Key findings

- A pro-angiogenic macrophage subset linked to NF-κB signaling is associated with worse clinical outcomes.
- An interferon-primed macrophage subset improves survival by recruiting T cells via CXCL9/10/11 secretion.
- CD8 T cells shift from anti-tumor to pro-tumor roles during cancer progression.

## Abstract

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.

This study presents a comprehensive single‐cell atlas of the immune landscape in gynaecological tumours. Angio‐Mac, driven by NFKB1, was associated with worse clinical outcomes. IFN‐Mac_CXCL9 improved survival by recruiting T cells through CXCL9/10/11 secretion. T cells experienced a shift from anti‐tumour to pro‐tumour during the progression of cancer.