Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma
Abstract 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...
| Main Authors: | , , , , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Wiley
2022-10-01
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| Series: | Advanced Science |
| Subjects: | |
| Online Access: | https://doi.org/10.1002/advs.202203040 |
| _version_ | 1811241305330679808 |
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| author | Zhihua Ou Shitong Lin Jiaying Qiu Wencheng Ding Peidi Ren Dongsheng Chen Jiaxuan Wang Yihan Tong Di Wu Ao Chen Yuan Deng Mengnan Cheng Ting Peng Haorong Lu Huanming Yang Jian Wang Xin Jin Ding Ma Xun Xu Yanzhou Wang Junhua Li Peng Wu |
| author_facet | Zhihua Ou Shitong Lin Jiaying Qiu Wencheng Ding Peidi Ren Dongsheng Chen Jiaxuan Wang Yihan Tong Di Wu Ao Chen Yuan Deng Mengnan Cheng Ting Peng Haorong Lu Huanming Yang Jian Wang Xin Jin Ding Ma Xun Xu Yanzhou Wang Junhua Li Peng Wu |
| author_sort | Zhihua Ou |
| collection | DOAJ |
| description | Abstract 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. |
| first_indexed | 2024-04-12T13:34:26Z |
| format | Article |
| id | doaj.art-17fadd43f70142cf85c07bc9cdf5c6ea |
| institution | Directory Open Access Journal |
| issn | 2198-3844 |
| language | English |
| last_indexed | 2024-04-12T13:34:26Z |
| publishDate | 2022-10-01 |
| publisher | Wiley |
| record_format | Article |
| series | Advanced Science |
| spelling | doaj.art-17fadd43f70142cf85c07bc9cdf5c6ea2022-12-22T03:31:04ZengWileyAdvanced Science2198-38442022-10-01929n/an/a10.1002/advs.202203040Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell CarcinomaZhihua Ou0Shitong Lin1Jiaying Qiu2Wencheng Ding3Peidi Ren4Dongsheng Chen5Jiaxuan Wang6Yihan Tong7Di Wu8Ao Chen9Yuan Deng10Mengnan Cheng11Ting Peng12Haorong Lu13Huanming Yang14Jian Wang15Xin Jin16Ding Ma17Xun Xu18Yanzhou Wang19Junhua Li20Peng Wu21BGI‐Zhenzhen Shenzhen 518083 ChinaCancer Biology Research Center (Key Laboratory of the Ministry of Education) Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaCancer Biology Research Center (Key Laboratory of the Ministry of Education) Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaDepartment of Obstetrics and Gynecology Southwest Hospital Third Military Medical University Chongqing 400038 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaCancer Biology Research Center (Key Laboratory of the Ministry of Education) Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaCancer Biology Research Center (Key Laboratory of the Ministry of Education) Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaDepartment of Obstetrics and Gynecology Southwest Hospital Third Military Medical University Chongqing 400038 ChinaBGI‐Zhenzhen Shenzhen 518083 ChinaCancer Biology Research Center (Key Laboratory of the Ministry of Education) Tongji Hospital Tongji Medical College Huazhong University of Science and Technology Wuhan 430000 ChinaAbstract 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.https://doi.org/10.1002/advs.202203040cancer‐associated fibroblastscervical cancersingle‐nucleus RNA sequencingspatial transcriptomicstumor microenvironment |
| spellingShingle | Zhihua Ou Shitong Lin Jiaying Qiu Wencheng Ding Peidi Ren Dongsheng Chen Jiaxuan Wang Yihan Tong Di Wu Ao Chen Yuan Deng Mengnan Cheng Ting Peng Haorong Lu Huanming Yang Jian Wang Xin Jin Ding Ma Xun Xu Yanzhou Wang Junhua Li Peng Wu Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma Advanced Science cancer‐associated fibroblasts cervical cancer single‐nucleus RNA sequencing spatial transcriptomics tumor microenvironment |
| title | Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma |
| title_full | Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma |
| title_fullStr | Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma |
| title_full_unstemmed | Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma |
| title_short | Single‐Nucleus RNA Sequencing and Spatial Transcriptomics Reveal the Immunological Microenvironment of Cervical Squamous Cell Carcinoma |
| title_sort | single nucleus rna sequencing and spatial transcriptomics reveal the immunological microenvironment of cervical squamous cell carcinoma |
| topic | cancer‐associated fibroblasts cervical cancer single‐nucleus RNA sequencing spatial transcriptomics tumor microenvironment |
| url | https://doi.org/10.1002/advs.202203040 |
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