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

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单位: [1]BGI Zhenzhen, Shenzhen 518083, Peoples R China [2]BGI Shenzhen, Shenzhen Key Lab Unknown Pathogen Identificat, Shenzhen 518083, Peoples R China [3]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Canc Biol Res Ctr,Key Lab,Minist Educ,Wuhan 430000,Peoples R China [4]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Gynecol Oncol,Wuhan 430000,Peoples R China [5]Univ Chinese Acad Sci, Coll Life Sci, Beijing 100049, Peoples R China [6]Northwest A&F Univ, Coll Innovat & Expt, Yangling 712100, Shaanxi, Peoples R China [7]Qingdao Univ, Sch Basic Med, Qingdao 266071, Peoples R China [8]Univ Copenhagen, Dept Biol, DK-2200 Copenhagen, Denmark [9]Third Mil Med Univ, Southwest Hosp, Dept Obstet & Gynecol, Chongqing 400038, Peoples R China [10]BGI Shenzhen, China Natl GeneBank, Shenzhen 518120, Peoples R China [11]Guangdong Prov Key Lab Genome Read & Write, Shenzhen 518120, Peoples R China [12]James D Watson Inst Genome Sci, Hangzhou 310058, Peoples R China
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关键词: cancer-associated fibroblasts cervical cancer single-nucleus RNA sequencing spatial transcriptomics tumor microenvironment

摘要:
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.

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出版当年[2021]版:
大类 | 1 区 材料科学
小类 | 1 区 纳米科技 1 区 材料科学:综合 2 区 化学综合
最新[2025]版:
大类 | 1 区 综合性期刊
小类 | 1 区 化学:综合 1 区 材料科学:综合 1 区 纳米科技
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出版当年[2020]版:
Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY Q1 CHEMISTRY, MULTIDISCIPLINARY
最新[2024]版:
Q1 CHEMISTRY, MULTIDISCIPLINARY Q1 MATERIALS SCIENCE, MULTIDISCIPLINARY Q1 NANOSCIENCE & NANOTECHNOLOGY

影响因子: 最新[2024版] 最新五年平均 出版当年[2020版] 出版当年五年平均 出版前一年[2019版] 出版后一年[2021版]

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第一作者单位: [1]BGI Zhenzhen, Shenzhen 518083, Peoples R China [2]BGI Shenzhen, Shenzhen Key Lab Unknown Pathogen Identificat, Shenzhen 518083, Peoples R China
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通讯机构: [1]BGI Zhenzhen, Shenzhen 518083, Peoples R China [2]BGI Shenzhen, Shenzhen Key Lab Unknown Pathogen Identificat, Shenzhen 518083, Peoples R China [3]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Canc Biol Res Ctr,Key Lab,Minist Educ,Wuhan 430000,Peoples R China [4]Huazhong Univ Sci & Technol,Tongji Med Coll,Tongji Hosp,Dept Gynecol Oncol,Wuhan 430000,Peoples R China [11]Guangdong Prov Key Lab Genome Read & Write, Shenzhen 518120, Peoples R China
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