单细胞RNA测序揭示宫颈癌放疗诱导肿瘤微环境的变化及肥大细胞免疫抑制的分子机制

IF 3.9 4区 生物学 Q1 GENETICS & HEREDITY
Lujiadai Xue, Linzhi Gao, Shimin Zhou, Chaofan Yan, Xian Zhang, Wei Lin, Hu Li, Yuan Shen, Xiaoyu Wang
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引用次数: 0

摘要

放射治疗(RT)是宫颈癌(CC)的重要治疗手段,可有效控制肿瘤生长,提高生存率。然而,放射治疗诱导的细胞异质性及其潜在机制尚不清楚,这可能会影响治疗效果。本研究旨在探讨CC放疗后肿瘤微环境的变化,以期为提高放疗效果提供依据。我们首次应用单细胞RNA测序(scRNA-seq)分析了三名CC患者放疗前后的组织样本。我们获得了52,506个细胞的基因表达数据,以确定放疗引起的细胞变化和分子机制。放疗显著改变肿瘤微环境(TME)内的细胞组成和基因表达,特别是上调肥大细胞的表达。肥大细胞在放疗后CC生态系统中涉及多个细胞轴,在肿瘤免疫抑制和基质重塑中发挥关键作用。scRNA-seq揭示了放疗后细胞类型之间的基因表达变化,强调了特定细胞类型在治疗后调节TME中的重要性。本研究揭示了CC放射治疗的分子机制及肥大细胞的作用,为优化CC的个性化治疗提供基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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

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.

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来源期刊
CiteScore
3.50
自引率
3.40%
发文量
92
审稿时长
2 months
期刊介绍: Functional & Integrative Genomics is devoted to large-scale studies of genomes and their functions, including systems analyses of biological processes. The journal will provide the research community an integrated platform where researchers can share, review and discuss their findings on important biological questions that will ultimately enable us to answer the fundamental question: How do genomes work?
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