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利用 Stereo-XCR-seq 揭示肺腺癌中肿瘤反应性淋巴细胞引发的异位类生发中心生态位

Uncovering ectopic GC-like niches for tumor reactive lymphocyte priming in lung adenocarcinoma using Stereo-XCR-seq.

期刊
Nature Communications
PMID
42547508
原文
PubMed ↗
发布日期

作者

  • Xiaojuan Zhan — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Mengye Huang — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Yang Zhang — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Zhong Liu — BGI Research, Shenzhen, China.
  • Chengwu Liu — Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • Yanying Guo — BGI Research, Shenzhen, China.
  • Yi Liu — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Wenwen Zhou — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Yixin Yan — BGI Research, Hangzhou, China.
  • Hui Zeng — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Yingqi Dong — Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Xuan Dong — BGI Research, Hangzhou, China.
  • Xiaoyu Chen — BGI Research, Hangzhou, China.
  • Haohang Yang — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Rong Ma — BGI Research, Hangzhou, China.
  • Fan Zhu — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Xubin Zheng — School of Computing and Information Technology, Great Bay University, Dongguan, China.
  • Xinxing Li — BGI Research, Hangzhou, China.
  • Sen Hou — Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
  • Zhidong Gao — Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
  • Jinwen Yin — Zhejiang University Liangzhu Laboratory, Hangzhou, China.
  • Francis Ka-Ming Chan — Zhejiang University Liangzhu Laboratory, Hangzhou, China.
  • Qin Wu — Zhejiang Cancer Hospital, Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
  • Senyi Deng — Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • Yin Yao — Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Shengbao Suo — Guangzhou National Laboratory, Guangzhou, China.
  • Chuanyu Liu — State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China.
  • Longqi Liu — BGI Research, Shenzhen, China.
  • Xun Xu — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Yong Hou — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Haoran Tao — BGI Research, Shenzhen, China.
  • Xinlei Ai — School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Yuliang Dong — BGI Research, Shenzhen, China.
  • Tao Zeng — BGI Research, Shenzhen, China.
  • Hanyong Sun — Department of Liver Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
  • Young Li — BGI Research, Shenzhen, China.
  • Li Zuo — Innovation and Entrepreneurship Laboratory for College Students, Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei, China.
  • Hua Wang — Laboratory Animal Center, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei, China.
  • Xin Liu — College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • Zhifang Wu — Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, China.
  • Jingying Zhou — BGI Research, Shenzhen, China. zhoujy@cuhk.edu.hk.
  • Zexian Zeng — Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. zexianzeng@pku.edu.cn.
  • Yu Feng — State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China. fengyu@suat-sz.edu.cn.

作者单位

  • College of Life Sciences, University of Chinese Academy of Sciences, Beijing, China.
  • BGI Research, Shenzhen, China.
  • Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • BGI Research, Hangzhou, China.
  • Department of Otolaryngology-Head and Neck Surgery, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • School of Computing and Information Technology, Great Bay University, Dongguan, China.
  • Department of Gastroenterological Surgery, Peking University People's Hospital, Beijing, China.
  • Zhejiang University Liangzhu Laboratory, Hangzhou, China.
  • Zhejiang Cancer Hospital, Key Laboratory of Zhejiang Province for Aptamers and Theranostics, Hangzhou Institute of Medicine (HIM), Chinese Academy of Sciences, Hangzhou, China.
  • Institute of Thoracic Oncology and Department of Thoracic Surgery, West China Hospital, Sichuan University, Chengdu, China.
  • Guangzhou National Laboratory, Guangzhou, China.
  • State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China.
  • School of Biomedical Sciences, The Chinese University of Hong Kong, Hong Kong SAR, China.
  • Department of Liver Surgery, Renji Hospital Affiliated to Shanghai Jiao Tong University, School of Medicine, Shanghai, China.
  • Innovation and Entrepreneurship Laboratory for College Students, Laboratory of Molecular Biology, Department of Biochemistry, Anhui Medical University, Hefei, China.
  • Laboratory Animal Center, Key Laboratory of Anti-inflammatory and Immune Medicine (Anhui Medical University), Ministry of Education, Hefei, China.
  • Shanxi Medical University-BGI Collaborative Center for Future Medicine, Shanxi Medical University, Taiyuan, China.
  • BGI Research, Shenzhen, China. zhoujy@cuhk.edu.hk.
  • Peking-Tsinghua Center for Life Sciences, Academy for Advanced Interdisciplinary Studies, Peking University, Beijing, China. zexianzeng@pku.edu.cn.
  • State Key Laboratory of Genome and Multi-omics Technologies, BGI Research, Shenzhen, China. fengyu@suat-sz.edu.cn.

摘要

中文

T/B 细胞受体（T/BCR）协调抗原靶向免疫反应，在抗肿瘤免疫反应中起关键作用。在单细胞分辨率下原位追踪 T 和 B 细胞克隆进化对于理解适应性免疫反应至关重要。为了解决缺乏原位单细胞 T/BCR（XCR）测序工具的问题，我们开发了 Stereo-XCR-seq，一种在亚细胞分辨率下从空间转录组 cDNA 文库中检索和测序 TCR 和 BCR 的高效方法。Stereo-XCR-seq 能够在大范围组织中高保真、无偏地恢复 XCR 序列以及空间转录组，有助于原位识别具有不同克隆活性的异质性淋巴聚集体。利用 Stereo-XCR-seq，我们在 11 个肺腺癌（LUAD）肿瘤中发现 IgG+ 浆细胞聚集体表现出异位生发中心样（GC-like）生态位的特征，从远端未成熟三级淋巴结构中筛选肿瘤反应性克隆。LUAD 中这些 IgG+ 浆细胞聚集体的存在表明改善了抗肿瘤免疫监视和对免疫检查点阻断（ICB）治疗的敏感性。总之，Stereo-XCR-seq 能够原位单细胞分析 T 和 B 细胞克隆活性及其与局部微环境的相互作用，将肿瘤反应性与淋巴细胞的肿瘤内分布联系起来，从而为剖析人类疾病中的淋巴细胞克隆动态提供了一个多功能工具。

English

T/B cell receptors (T/BCR), coordinating antigen-targeting immune response, play crucial roles in anti-tumor immune response. Tracking T and B cell clonal evolution in situ at single-cell resolution is essential for understanding the adaptive immune responses. To address the lack of tools for in situ single-cell T/BCR (XCR) sequencing, we develop Stereo-XCR-seq, an efficient method for retrieving and sequencing TCR and BCR from spatial transcriptome cDNA libraries at subcellular resolution. Stereo-XCR-seq enables high-fidelity, unbiased recovery of XCR sequences alongside spatial transcriptomics in extensive tissues, facilitating the identification of heterogeneous lymphoid aggregates with distinct clonal activities in situ. Using Stereo-XCR-seq, we uncover that IgG+ plasma cell aggregates display features of ectopic germinal center-like (GC-like) niches to select tumor-reactive clones from distal immature tertiary lymphoid structures in 11 lung adenocarcinoma (LUAD) tumors. The presence of these IgG+ plasma cell aggregates in LUAD indicates an improved anti-tumor immune surveillance and sensitivity towards immune checkpoint blockade (ICB) therapy. Collectively, Stereo-XCR-seq enables in situ single-cell profiling of T and B cell clonal activities and their interactions with local microenvironment, links tumor reactivity to intratumoral distribution of lymphocytes, and thus offers a versatile tool for dissecting lymphocyte clonal dynamics across human diseases.

分类与指标

研究类型
基础研究
病种
肺癌
JCR 分区
Q1
影响因子
18.1
新锐分区
1区