TY - JOUR
T1 - Single-Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma
AU - Ou, Zhihua
AU - Lin, Shitong
AU - Qiu, Jiaying
AU - Ding, Wencheng
AU - Ren, Peidi
AU - Chen, Dongsheng
AU - Wang, Jiaxuan
AU - Tong, Yihan
AU - Wu, Di
AU - Chen, Ao
AU - Deng, Yuan
AU - Cheng, Mengnan
AU - Peng, Ting
AU - Lu, Haorong
AU - Yang, Huanming
AU - Wang, Jian
AU - Jin, Xin
AU - Ma, Ding
AU - Xu, Xun
AU - Wang, Yanzhou
AU - Li, Junhua
AU - Wu, Peng
N1 - Publisher Copyright:
© 2022 The Authors. Advanced Science published by Wiley-VCH GmbH.
PY - 2022/10/14
Y1 - 2022/10/14
N2 - 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.
AB - 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.
KW - cancer-associated fibroblasts
KW - cervical cancer
KW - single-nucleus RNA sequencing
KW - spatial transcriptomics
KW - tumor microenvironment
UR - https://www.scopus.com/pages/publications/85136470749
U2 - 10.1002/advs.202203040
DO - 10.1002/advs.202203040
M3 - 文章
C2 - 35986392
AN - SCOPUS:85136470749
SN - 2198-3844
VL - 9
JO - Advanced Science
JF - Advanced Science
IS - 29
M1 - 2203040
ER -
可持续发展目标 3 良好健康与福祉