Single‐cell dissection of cervical cancer reveals key subsets of the tumor immune microenvironment

Author:

Cao Guangxu1ORCID,Yue Jiali2ORCID,Ruan Yetian1ORCID,Han Ya2,Zhi Yong1,Lu Jianqiao1,Liu Min1ORCID,Xu Xinxin1,Wang Jin1,Gu Quan3ORCID,Wen Xuejun4,Gao Jinli5,Zhang Qingfeng2ORCID,Kang Jiuhong6ORCID,Wang Chenfei2ORCID,Li Fang1ORCID

Affiliation:

1. Department of Obstetrics and Gynecology, Shanghai East Hospital, School of Medicine Tongji University Shanghai China

2. Key Laboratory of Spine and Spinal Cord Injury Repair and Regeneration of Ministry of Education, Department of Orthopedics, Tongji Hospital, Frontier Science Center for Stem Cells, School of Life Science and Technology Tongji University Shanghai China

3. CVR Bioinformatics University of Glasgow Centre for Virus Research Glasgow UK

4. Department of Chemical and Life Science Engineering, School of Engineering Virginia Commonwealth University Richmond Virginia USA

5. Department of Pathology, Shanghai East Hospital, School of Medicine Tongji University Shanghai China

6. Clinical and Translational Research Center of Shanghai First Maternity and Infant Hospital, Shanghai Key Laboratory of Signaling and Disease Research, Collaborative Innovation Center for Brain Science, School of Life Sciences and Technology Tongji University Shanghai China

Abstract

AbstractThe tumor microenvironment (TME) directly determines patients' outcomes and therapeutic efficiencies. An in‐depth understanding of the TME is required to improve the prognosis of patients with cervical cancer (CC). This study conducted single‐cell RNA and TCR sequencing of six‐paired tumors and adjacent normal tissues to map the CC immune landscape. T and NK cells were highly enriched in the tumor area and transitioned from cytotoxic to exhaustion phenotypes. Our analyses suggest that cytotoxic large‐clone T cells are critical effectors in the antitumor response. This study also revealed tumor‐specific germinal center B cells associated with tertiary lymphoid structures. A high‐germinal center B cell proportion in patients with CC is predictive of improved clinical outcomes and is associated with elevated hormonal immune responses. We depicted an immune‐excluded stromal landscape and established a joint model of tumor and stromal cells to predict CC patients' prognosis. The study revealed tumor ecosystem subsets linked to antitumor response or prognosis in the TME and provides information for future combinational immunotherapy.

Funder

National Natural Science Foundation of China

Natural Science Foundation of Shanghai

Shanghai Science and Technology Development Foundation

Publisher

Springer Science and Business Media LLC

Subject

General Immunology and Microbiology,General Biochemistry, Genetics and Molecular Biology,Molecular Biology,General Neuroscience

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