Single-cell RNA sequencing revealed changes in the tumor microenvironment induced by radiotherapy for cervical cancer and the molecular mechanism of mast cells in immunosuppression

Abstract

Radiotherapy (RT) is an important treatment for cervical cancer (CC), effectively controlling tumor growth and improving survival rates. However, radiotherapy-induced cell heterogeneity and its underlying mechanisms remain unclear, which may potentially impact treatment efficacy. This study aims to investigate tumor microenvironment changes following radiotherapy for CC, hoping to provide evidence to improve the therapeutic effects of radiotherapy. For the first time, we applied single-cell RNA sequencing (scRNA-seq) to analyze tissue samples from three CC patients pre- and post-radiotherapy. We obtained gene expression data from 52,506 cells to identify the cellular changes and molecular mechanisms induced by radiotherapy. Radiotherapy significantly alters cellular composition and gene expression within the tumor microenvironment (TME), notably upregulating mast cell expression. Mast cells are involved in multiple cell axes in the CC ecosystem after radiotherapy, and play a pivotal role in tumor immunosuppression and matrix remodeling. scRNA-seq revealed gene expression variations among cell types after radiotherapy, underscoring the importance of specific cell types in modulating the TME post-treatment. This study revealed the molecular mechanism of radiotherapy for CC and the role of mast cells, providing a foundation for optimizing the personalized treatment of CC.