Single-Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma

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  • Zhihua Ou
  • Shitong Lin
  • Jiaying Qiu
  • Wencheng Ding
  • Peidi Ren
  • Dongsheng Chen
  • Jiaxuan Wang
  • Yihan Tong
  • Di Wu
  • Yuan Deng
  • Mengnan Cheng
  • Ting Peng
  • Haorong Lu
  • Huanming Yang
  • Jian Wang
  • Xin Jin
  • Ding Ma
  • Xun Xu
  • Yanzhou Wang
  • Junhua Li
  • Peng Wu

The effective treatment of advanced cervical cancer remains challenging. Herein, single-nucleus RNA sequencing (snRNA-seq) and SpaTial enhanced resolution omics-sequencing (Stereo-seq) are used to investigate the immunological microenvironment of cervical squamous cell carcinoma (CSCC). The expression levels of most immune suppressive genes in the tumor and inflammation areas of CSCC are not significantly higher than those in the non-cancer samples, except for LGALS9 and IDO1. Stronger signals of CD56+ NK cells and immature dendritic cells are found in the hypermetabolic tumor areas, whereas more eosinophils, immature B cells, and Treg cells are found in the hypometabolic tumor areas. Moreover, a cluster of pro-tumorigenic cancer-associated myofibroblasts (myCAFs) are identified. The myCAFs may support the growth and metastasis of tumors by inhibiting lymphocyte infiltration and remodeling of the tumor extracellular matrix. Furthermore, these myCAFs are associated with poorer survival probability in patients with CSCC, predict resistance to immunotherapy, and might be present in a small fraction (< 30%) of patients with advanced cancer. Immunohistochemistry and multiplex immunofluorescence staining are conducted to validate the spatial distribution and potential function of myCAFs. Collectively, these findings enhance the understanding of the immunological microenvironment of CSCC and shed light on the treatment of advanced CSCC.

Original languageEnglish
Article number2203040
JournalAdvanced Science
Volume9
Issue number29
Number of pages20
ISSN2198-3844
DOIs
Publication statusPublished - 2022

Bibliographical note

Publisher Copyright:
© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.

    Research areas

  • cancer-associated fibroblasts, cervical cancer, single-nucleus RNA sequencing, spatial transcriptomics, tumor microenvironment

ID: 318805083