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文献精选 > 近年高分"单细胞测序"研究（IF≥30，近5年）

Deciphering and advancing CAR T-cell therapy with single-cell sequencing technologies. ​

文献信息 ​

DOI10.1186/s12943-023-01783-1
PMID37149643
期刊Molecular cancer
影响因子33.9
JCR 分区Q1
发表年份2023
被引次数18
关键词生物学, CAR T细胞, 机制, 单细胞测序技术, 策略
文献类型Journal Article, Review, Research Support, Non-U.S. Gov't
ISSN1476-4598
页码80
期号22(1)
作者Shengkang Huang, Xinyu Wang, Yu Wang, Yajing Wang, Chenglong Fang, Yazhuo Wang, Sifei Chen, Runkai Chen, Tao Lei, Yuchen Zhang, Xinjie Xu, Yuhua Li

一句话小结 ​

本综述探讨了单细胞测序技术在CAR T细胞治疗中的应用，揭示了其在理解生物学特征、临床反应和不良事件机制方面的重要贡献。研究提出了一种多组学研究模式，以推动CAR T细胞治疗的优化和靶点选择，旨在克服当前面临的挑战，促进其临床应用。

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生物学 · CAR T细胞 · 机制 · 单细胞测序技术 · 策略

摘要 ​

嵌合抗原受体（CAR）T细胞治疗在癌症免疫治疗领域取得了显著进展，但一些机制不明的挑战阻碍了其广泛的临床应用。单细胞测序技术以其对细胞异质性和分子模式进行无偏分析的强大能力，极大地推动了我们对免疫学和肿瘤学的理解。在本综述中，我们总结了单细胞测序技术在CAR T细胞治疗中的最新应用，包括生物学特征、临床反应和不良事件的最新机制、有前景的策略以及对CAR T细胞治疗和CAR靶点选择的发展贡献。总体而言，我们提出了一种多组学研究模式，以指导未来对CAR T细胞治疗的潜在研究。

英文摘要 ​

Chimeric antigen receptor (CAR) T-cell therapy has made remarkable progress in cancer immunotherapy, but several challenges with unclear mechanisms hinder its wide clinical application. Single-cell sequencing technologies, with the powerful unbiased analysis of cellular heterogeneity and molecular patterns at unprecedented resolution, have greatly advanced our understanding of immunology and oncology. In this review, we summarize the recent applications of single-cell sequencing technologies in CAR T-cell therapy, including the biological characteristics, the latest mechanisms of clinical response and adverse events, promising strategies that contribute to the development of CAR T-cell therapy and CAR target selection. Generally, we propose a multi-omics research mode to guide potential future research on CAR T-cell therapy.

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主要研究问题 ​

  1. 单细胞测序技术如何帮助识别CAR T细胞治疗中的生物标志物？
  2. 在CAR T细胞治疗的临床应用中，单细胞测序技术揭示了哪些新的机制？
  3. 有哪些策略可以优化CAR T细胞的靶点选择，以提高治疗效果？
  4. 单细胞测序技术如何促进我们对CAR T细胞治疗不良事件的理解？
  5. 多组学研究模式在CAR T细胞治疗中的应用前景如何？

核心洞察 ​

研究背景和目的 ​

CAR T细胞疗法在癌症免疫治疗中取得了显著进展，尤其是在血液恶性肿瘤的治疗上。然而，许多机制不清晰的挑战限制了其广泛应用。单细胞测序技术的出现，提供了对细胞异质性和分子模式的无偏见分析，极大地推动了我们对免疫学和肿瘤学的理解。本研究旨在总结单细胞测序技术在CAR T细胞疗法中的应用，包括其生物特征、临床反应机制及不良事件，并提出多组学研究模式以指导未来的研究。

主要方法/材料/实验设计 ​

研究采用了单细胞RNA测序（scRNA-seq）、单细胞T细胞受体测序（scTCR-seq）、单细胞转录组和表观基因组测序（scATAC-seq）等多种单细胞测序技术。以下是研究的技术路线图：

Mermaid diagram

关键结果和发现 ​

  1. CAR T细胞异质性：研究表明，CAR T细胞产品的异质性受CAR结构、T细胞亚型和生产过程的影响。不同的成本刺激域（如CD28与4-1BB）导致CAR T细胞在临床效果和基因表达上的差异。
  2. 细胞动态：在CAR T细胞输注后，CD4+和CD8+ T细胞表现出不同的增殖和分化轨迹，且与临床反应密切相关。
  3. 免疫微环境：CAR T细胞与肿瘤细胞及内源性免疫细胞之间的相互作用显著影响CAR T细胞的功能和耐受性，单细胞测序技术帮助揭示了这一过程中的复杂机制。

主要结论/意义/创新性 ​

本研究强调了单细胞测序技术在理解CAR T细胞疗法中的重要性，尤其是在揭示细胞异质性、动态变化及其与肿瘤微环境相互作用的机制方面。提出的多组学研究模式有助于系统性分析CAR T细胞的生物学特性，并为未来的临床应用提供指导。

研究局限性和未来方向 ​

研究指出单细胞测序技术在覆盖度和深度方面的局限，且现有的分析方法仍需优化。未来的研究应集中于：

  1. 提高单细胞测序的准确性和重复性，建立标准化的数据分析流程。
  2. 扩大临床样本库，以支持多组学的深入研究。
  3. 探索新的CAR靶点，以提高治疗的特异性和有效性。

通过这些努力，单细胞测序技术将为CAR T细胞疗法的优化和精准医疗的推进提供重要支持。

参考文献 ​

  1. Enhanced CAR T cell expansion and prolonged persistence in pediatric patients with ALL treated with a low-affinity CD19 CAR. - Sara Ghorashian;Anne Marijn Kramer;Shimobi Onuoha;Gary Wright;Jack Bartram;Rachel Richardson;Sarah J Albon;Joan Casanovas-Company;Fernanda Castro;Bilyana Popova;Krystle Villanueva;Jenny Yeung;Winston Vetharoy;Aleks Guvenel;Patrycja A Wawrzyniecka;Leila Mekkaoui;Gordon Weng-Kit Cheung;Danielle Pinner;Jan Chu;Giovanna Lucchini;Juliana Silva;Oana Ciocarlie;Arina Lazareva;Sarah Inglott;Kimberly C Gilmour;Gulrukh Ahsan;Mathieu Ferrari;Somayya Manzoor;Kim Champion;Tony Brooks;Andre Lopes;Allan Hackshaw;Farzin Farzaneh;Robert Chiesa;Kanchan Rao;Denise Bonney;Sujith Samarasinghe;Nicholas Goulden;Ajay Vora;Paul Veys;Rachael Hough;Robert Wynn;Martin A Pule;Persis J Amrolia - Nature medicine (2019)
  2. IFNγ Is Critical for CAR T Cell-Mediated Myeloid Activation and Induction of Endogenous Immunity. - Darya Alizadeh;Robyn A Wong;Sharareh Gholamin;Madeleine Maker;Maryam Aftabizadeh;Xin Yang;Joseph R Pecoraro;John D Jeppson;Dongrui Wang;Brenda Aguilar;Renate Starr;Claire B Larmonier;Nicolas Larmonier;Min-Hsuan Chen;Xiwei Wu;Antoni Ribas;Behnam Badie;Stephen J Forman;Christine E Brown - Cancer discovery (2021)
  3. Tisagenlecleucel in Children and Young Adults with B-Cell Lymphoblastic Leukemia. - Shannon L Maude;Theodore W Laetsch;Jochen Buechner;Susana Rives;Michael Boyer;Henrique Bittencourt;Peter Bader;Michael R Verneris;Heather E Stefanski;Gary D Myers;Muna Qayed;Barbara De Moerloose;Hidefumi Hiramatsu;Krysta Schlis;Kara L Davis;Paul L Martin;Eneida R Nemecek;Gregory A Yanik;Christina Peters;Andre Baruchel;Nicolas Boissel;Francoise Mechinaud;Adriana Balduzzi;Joerg Krueger;Carl H June;Bruce L Levine;Patricia Wood;Tetiana Taran;Mimi Leung;Karen T Mueller;Yiyun Zhang;Kapildeb Sen;David Lebwohl;Michael A Pulsipher;Stephan A Grupp - The New England journal of medicine (2018)
  4. Characteristics of anti-CD19 CAR T cell infusion products associated with efficacy and toxicity in patients with large B cell lymphomas. - Qing Deng;Guangchun Han;Nahum Puebla-Osorio;Man Chun John Ma;Paolo Strati;Beth Chasen;Enyu Dai;Minghao Dang;Neeraj Jain;Haopeng Yang;Yuanxin Wang;Shaojun Zhang;Ruiping Wang;Runzhe Chen;Jordan Showell;Sreejoyee Ghosh;Sridevi Patchva;Qi Zhang;Ryan Sun;Frederick Hagemeister;Luis Fayad;Felipe Samaniego;Hans C Lee;Loretta J Nastoupil;Nathan Fowler;R Eric Davis;Jason Westin;Sattva S Neelapu;Linghua Wang;Michael R Green - Nature medicine (2020)
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  6. Mechanisms underlying CD19-positive ALL relapse after anti-CD19 CAR T cell therapy and associated strategies. - Yuru Nie;Weiqing Lu;Daiyu Chen;Huilin Tu;Zhenling Guo;Xuan Zhou;Meifang Li;Sanfang Tu;Yuhua Li - Biomarker research (2020)
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引用本文的文献 ​

  1. Revolutionizing cancer immunotherapy in solid tumor: CAR engineering and single-cell sequencing insights. - Zuhui Pu;Tony Bowei Wang;Lisha Mou - Frontiers in immunology (2023)
  2. Harnessing the Transcriptional Signatures of CAR-T-Cells and Leukemia/Lymphoma Using Single-Cell Sequencing Technologies. - Yu-Mei Liao;Shih-Hsien Hsu;Shyh-Shin Chiou - International journal of molecular sciences (2024)
  3. Neural Network-Based Filter Design for Compressive Raman Classification of Cells. - Stefan Semrau - Journal of chemical information and modeling (2024)
  4. Single-cell RNA sequencing in ovarian cancer: revealing new perspectives in the tumor microenvironment. - Qiannan Zhao;Huaming Shao;Tianmei Zhang - American journal of translational research (2024)
  5. Role of N6-methyladenosine RNA modification in cancer. - Yi Qu;Nannan Gao;Shengwei Zhang;Limin Gao;Bing He;Chao Wang;Chunli Gong;Qiuyue Shi;Zhibin Li;Shiming Yang;Yufeng Xiao - MedComm (2024)
  6. Recover then aggregate: unified cross-modal deep clustering with global structural information for single-cell data. - Ziyi Wang;Peng Luo;Mingming Xiao;Boyang Wang;Tianyu Liu;Xiangyu Sun - Briefings in bioinformatics (2024)
  7. Leveraging CRISPR gene editing technology to optimize the efficacy, safety and accessibility of CAR T-cell therapy. - Tao Lei;Yazhuo Wang;Yuchen Zhang;Yufei Yang;Jiaying Cao;Jiansong Huang;Jiali Chen;Huajing Chen;Jiayi Zhang;Luzheng Wang;Xinjie Xu;Robert Peter Gale;Liang Wang - Leukemia (2024)
  8. Immunofluorescence-Verified Sphingolipid Signatures Indicate Improved Prognosis in Liver Cancer Patients. - Lujuan Pan;Huijuan Huang;Pengpeng Zhang;Hua Li;Libai Lu;Mingwei Wei;Pin Zheng;Qi Wang;Junyu Guo;Yueqiu Qin - Journal of Cancer (2024)
  9. Advances and applications in single-cell and spatial genomics. - Jingjing Wang;Fang Ye;Haoxi Chai;Yujia Jiang;Teng Wang;Xia Ran;Qimin Xia;Ziye Xu;Yuting Fu;Guodong Zhang;Hanyu Wu;Guoji Guo;Hongshan Guo;Yijun Ruan;Yongcheng Wang;Dong Xing;Xun Xu;Zemin Zhang - Science China. Life sciences (2025)
  10. Role of CD4+ T cells in cancer immunity: a single-cell sequencing exploration of tumor microenvironment. - Qi An;Li Duan;Yuanyuan Wang;Fuxin Wang;Xiang Liu;Chao Liu;Qinyong Hu - Journal of translational medicine (2025)

... (8 更多 篇文献)

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