Single-cell RNA-sequencing reveals radiochemotherapy-induced innate immune activation and MHC-II upregulation in cervical cancer

单细胞 RNA 测序揭示宫颈癌放化疗诱导的先天免疫激活和 MHC-II 上调

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作者:Chao Liu, Xiaohui Li, Qingyu Huang, Min Zhang, Tianyu Lei, Fuhao Wang, Wenxue Zou, Rui Huang, Xiaoyu Hu, Cong Wang, Xiaoling Zhang, Bing Sun, Ligang Xing, Jinbo Yue, Jinming Yu3

Abstract

Radiochemotherapy (RCT) is a powerful treatment for cervical cancer, which affects not only malignant cells but also the immune and stromal compartments of the tumor. Understanding the remodeling of the local ecosystem induced by RCT would provide valuable insights into improving treatment strategies for cervical cancer. In this study, we applied single-cell RNA-sequencing to paired pre- and post-RCT tumor biopsies from patients with cervical cancer and adjacent normal cervical tissues. We found that the residual population of epithelial cells post-RCT showed upregulated expression of MHC class II genes. Moreover, RCT led to the accumulation of monocytic myeloid-derived suppressor cells with increased pro-inflammatory features and CD16+ NK cells with a higher cytotoxic gene expression signature. However, subclusters of T cells showed no significant increase in the expression of cytotoxic features post-RCT. These results reveal the complex responses of the tumor ecosystem to RCT, providing evidence of activation of innate immunity and MHC-II upregulation in cervical cancer.

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