# Chemoresistance Evolution in Ovarian Cancer Delineated by Single-Cell RNA Sequencing

## TL;DR

This study uses single-cell RNA sequencing to show how chemotherapy reshapes the tumor microenvironment in ovarian cancer, affecting immune cells and cancer progression.

## Contribution

The study reveals site-dependent transcriptional reprogramming of tumor cell clusters after chemotherapy using single-cell data.

## Key findings

- Chemotherapy reduces HLA diversity and increases PDCD1/CD274 in specific immune cell types.
- Cancer.cell.2 and CAF_C3 show stronger interactions in post-chemotherapy samples, linked to poor outcomes.
- Chemotherapy alters pre-existing cell clusters in a site-specific manner, influencing tumor progression.

## Abstract

High-grade serous ovarian cancer (HGSOC) is an aggressive gynecological malignancy characterized by intraperitoneal spread and chemotherapy resistance. Chemotherapies have demonstrated limited effectiveness in HGSOC, underscoring the urgent need to evaluate how the tumor microenvironment (TME) was reshaped by chemotherapy in different sites of tumor foci. In this study, we performed single-cell transcriptomic analysis to explore the TME in samples obtained from various sites of tumor foci, with or without the history of Neoadjuvant chemotherapy (NACT). We discovered that chemotherapy reshaped the tumor immune microenvironment, evident through the reduction in human leukocyte antigen (HLA) diversity and the increase in PDCD1/CD274 in CD8_ANXA1, LAMP3+ dendritic cell (DC_LAMP3), and EREG+ monocytes (mono_EREG). Moreover, cancer.cell.2, cancer-associated C3+ fibroblasts (CAF_C3), and Fibrocyte_CD34, which are prone to accumulate in the metastatic site and post-NACT group, harbored poor clinical outcome, reflected in the immune exclusion and tumor progression signaling. Cell–cell communication identified a stronger interaction between cancer.cell.2 and CAF_C3, as well as Fibrocyte_CD34, in post-NACT samples, indicating that chemotherapy reshapes pre-existing cell clusters in a site-dependent manner. Our findings suggest that chemotherapy and sites of foci were critical for the transcriptional reprogramming of pre-existed cell clusters. Our study offers a single-cell phenotype data substrate from which to develop a personalized combination of chemotherapy and immunotherapy.