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Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance

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收录情况： ◇ SCIE ◇ 自然指数

作者：
Fan Junpeng[1,2] * ; Lu Funian[1,2] * ; Qin Tianyu[1,2] * ; Peng Wenju[1,2] * ; Zhuang Xucui[1,2] ; Li Yinuo[1,2] ; Hou Xin[1,2] ; Fang Zixuan[1,2] ; Yang Yunyi[1,2] ; Guo Ensong[1,2] ; Yang Bin[1,2] ; Li Xi[1,2] ; Fu Yu[1,2] ; Kang Xiaoyan[1,2] ; Wu Zimeng[1,2] ; Han Lili[3] ; Mills Gordon B[4,5] ; Ma Xiangyi[1,2] ; Li Kezhen[1,2] ; Wu Peng[2,6] ; Ma Ding[1,2] ; Chen Gang[1,2] ; Sun Chaoyang[1,2] ;
单位： [1]Department of Gynecological Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]National Clinical Research Center for Obstetrics and Gynecology,Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [3]Department of Gynecology, People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi, China [4]Division of Oncological Sciences, Oregon Health and Sciences University, Portland, OR, USA [5]Knight Cancer Institute, Portland, OR, USA [6]Department of Gynecological Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
出处：
DOI： 10.1038/s41588-023-01570-0
ISSN：

摘要：
Cervical squamous cell carcinoma (CSCC) exhibits a limited response to immune-checkpoint blockade. Here we conducted a multiomic analysis encompassing single-cell RNA sequencing, spatial transcriptomics and spatial proteomics, combined with genetic and pharmacological perturbations to systematically develop a high-resolution and spatially resolved map of intratumoral expression heterogeneity in CSCC. Three tumor states (epithelial-cytokeratin, epithelial-immune (Epi-Imm) and epithelial senescence), recapitulating different stages of squamous differentiation, showed distinct tumor immune microenvironments. Bidirectional interactions between epithelial-cytokeratin malignant cells and immunosuppressive cancer-associated fibroblasts form an immune exclusionary microenvironment through transforming growth factor β pathway signaling mediated by FABP5. In Epi-Imm tumors, malignant cells interact with natural killer and T cells through interferon signaling. Preliminary analysis of samples from a cervical cancer clinical trial ( NCT04516616 ) demonstrated neoadjuvant chemotherapy induces a state transition to Epi-Imm, which correlates with pathological complete remission following treatment with immune-checkpoint blockade. These findings deepen the understanding of cellular state diversity in CSCC.© 2023. The Author(s), under exclusive licence to Springer Nature America, Inc.

基金：
National Natural Science Foundation of China (grant no. 82141106 to D.M., grant no. 82073259 to G.C. and grant no. 81974408 to C.S.), the Key R&D Program of Hubei Province (grant no. 2023BCB023 to C.S.) and Chen Xiao-ping Foundation for the Development of Science and Technology of Hubei Province (grant no. CXPJJH122006-1006 to B.Y.).
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外文
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出版当年[2022]版：
大类 | 1 区 生物学
小类 | 1 区 遗传学
最新[2025]版：
大类 | 1 区 生物学
小类 | 1 区 遗传学
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出版当年[2021]版：
Q1 GENETICS & HEREDITY
最新[2024]版：
Q1 GENETICS & HEREDITY

影响因子： 最新[2024版] 最新五年平均 出版当年[2021版] 出版当年五年平均 出版前一年[2020版] 出版后一年[2022版]

第一作者：
第一作者单位： [1]Department of Gynecological Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]National Clinical Research Center for Obstetrics and Gynecology,Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China
共同第一作者：
通讯作者：
通讯机构： [1]Department of Gynecological Oncology,Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [2]National Clinical Research Center for Obstetrics and Gynecology,Cancer Biology Research Center (Key Laboratory of the Ministry of Education),Tongji Hospital,Tongji Medical College,Huazhong University of Science and Technology,Wuhan,China [6]Department of Gynecological Oncology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China
推荐引用方式(GB/T 7714)：
Fan Junpeng,Lu Funian,Qin Tianyu,et al.Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance[J].NATURE GENETICS.2023,55(12):2175-2188.doi:10.1038/s41588-023-01570-0.
APA：
Fan Junpeng,Lu Funian,Qin Tianyu,Peng Wenju,Zhuang Xucui...&Sun Chaoyang.(2023).Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance.NATURE GENETICS,55,(12)
MLA：
Fan Junpeng,et al."Multiomic analysis of cervical squamous cell carcinoma identifies cellular ecosystems with biological and clinical relevance".NATURE GENETICS 55..12(2023):2175-2188

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