Single-cell transcriptomic analysis reveals intra-tumoral heterogeneity and immunotherapy strategies in high-grade serous ovarian cancer

TL;DR

This study uses single-cell RNA sequencing to uncover cell diversity in ovarian cancer and identifies immune-related cell types linked to better patient outcomes.

Contribution

The study reveals how IFIT1+ epithelial cells enhance immune response and identifies potential biomarkers for HGSOC treatment.

Findings

Seven major cell types were identified in high-grade serous ovarian cancer.

IFIT1+ epithelial cells overexpressing MHC class I are associated with improved patient prognosis.

Tumor-associated fibroblasts and epithelial cells contribute to chemoresistance and metastasis.

Abstract

High-grade serous ovarian cancer (HGSOC) is the most common type of ovarian cancer, characterized by high intra-tumoral heterogeneity and platinum resistance. In this study, single-cell RNA sequencing data with HGSOC were analyzed. We identified seven major cell types in HGSOC and observed significant changes in the proportions of cancer-associated fibroblasts and epithelial cells as tumor drug resistance increased. The abundance of IFIT1+ and CXCL10+ epithelial cells highly expressing MHC class Ⅰ molecules, which are strongly associated with antigen processing and presentation, was found to improve patients’ outcomes. Ultimately, the relationships between IFIT1, MHC class Ⅰ molecules, and CD8+ T cells were verified in additional cohorts, using multiplex immunohistochemistry. Our data suggest that IFIT1+ epithelial cells might enhance immune surveillance via increasing the expression of MHC class Ⅰ molecules and activating CD8+ T cells. Our findings provide a valuable resource for deciphering intra-tumoral heterogeneity and mechanisms driving the aggressiveness of HGSOC, revealing potential biomarkers for anti-cancer treatment.

•A single-cell RNA-seq atlas reveals extensive intra-tumoral heterogeneity in HGSOC•Tumor-associated fibroblasts and epithelial cells promote chemoresistance and metastasis•IFIT1+ epithelial cells overexpressing MHC class Ⅰ are associated with good prognosis

A single-cell RNA-seq atlas reveals extensive intra-tumoral heterogeneity in HGSOC

Tumor-associated fibroblasts and epithelial cells promote chemoresistance and metastasis

IFIT1+ epithelial cells overexpressing MHC class Ⅰ are associated with good prognosis

Cancer; Microenvironment; Transcriptomics

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