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单细胞 RNA 测序揭示了放化疗诱导的宫颈癌固有免疫激活和 MHC-II 上调。

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

机构信息

Department of Radiation Oncology and Shandong Provincial Key Laboratory of Radiation Oncology, Shandong Cancer Hospital and Institute, Shandong First Medical University and Shandong Academy of Medical Sciences, Jinan, 250117, China.

Research Unit of Radiation Oncology, Chinese Academy of Medical Sciences, Jinan, 250117, China.

出版信息

Signal Transduct Target Ther. 2023 Jan 30;8(1):44. doi: 10.1038/s41392-022-01264-9.

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.

摘要

放化疗(RCT)是治疗宫颈癌的有力手段,它不仅会影响恶性细胞,还会影响肿瘤的免疫和基质部分。了解 RCT 诱导的局部生态系统重塑,将为改善宫颈癌的治疗策略提供有价值的见解。在这项研究中,我们应用单细胞 RNA 测序,对宫颈癌患者和相邻正常宫颈组织的 RCT 前后配对肿瘤活检进行了分析。我们发现,RCT 后残留的上皮细胞群体表现出 MHC Ⅱ类基因的上调表达。此外,RCT 导致具有更高促炎特征的单核细胞髓样来源的抑制细胞和具有更高细胞毒性基因表达特征的 CD16 NK 细胞积累。然而,RCT 后 T 细胞亚群的细胞毒性特征表达并没有显著增加。这些结果揭示了肿瘤生态系统对 RCT 的复杂反应,为宫颈癌中固有免疫的激活和 MHC-II 的上调提供了证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/8177/9884664/cc134ee1d436/41392_2022_1264_Fig1_HTML.jpg

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