通过配对单细胞分析揭示早期肺腺癌的固有免疫格局

Innate Immune Landscape in Early Lung Adenocarcinoma by Paired Single-Cell Analyses.

作者信息

Lavin Yonit, Kobayashi Soma, Leader Andrew, Amir El-Ad David, Elefant Naama, Bigenwald Camille, Remark Romain, Sweeney Robert, Becker Christian D, Levine Jacob H, Meinhof Klaus, Chow Andrew, Kim-Shulze Seunghee, Wolf Andrea, Medaglia Chiara, Li Hanjie, Rytlewski Julie A, Emerson Ryan O, Solovyov Alexander, Greenbaum Benjamin D, Sanders Catherine, Vignali Marissa, Beasley Mary Beth, Flores Raja, Gnjatic Sacha, Pe'er Dana, Rahman Adeeb, Amit Ido, Merad Miriam

机构信息

Department of Oncological Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

The Precision Immunology Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Tisch Cancer Institute, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.

出版信息

Cell. 2017 May 4;169(4):750-765.e17. doi: 10.1016/j.cell.2017.04.014.

Abstract

To guide the design of immunotherapy strategies for patients with early stage lung tumors, we developed a multiscale immune profiling strategy to map the immune landscape of early lung adenocarcinoma lesions to search for tumor-driven immune changes. Utilizing a barcoding method that allows a simultaneous single-cell analysis of the tumor, non-involved lung, and blood cells, we provide a detailed immune cell atlas of early lung tumors. We show that stage I lung adenocarcinoma lesions already harbor significantly altered T cell and NK cell compartments. Moreover, we identified changes in tumor-infiltrating myeloid cell (TIM) subsets that likely compromise anti-tumor T cell immunity. Paired single-cell analyses thus offer valuable knowledge of tumor-driven immune changes, providing a powerful tool for the rational design of immune therapies. VIDEO ABSTRACT.

摘要

为指导早期肺癌患者免疫治疗策略的设计,我们开发了一种多尺度免疫分析策略,以描绘早期肺腺癌病变的免疫格局,寻找肿瘤驱动的免疫变化。利用一种条形码方法,可同时对肿瘤、未受累肺组织和血细胞进行单细胞分析,我们提供了早期肺肿瘤详细的免疫细胞图谱。我们发现,I期肺腺癌病变中T细胞和NK细胞区室已经发生了显著改变。此外,我们还确定了肿瘤浸润髓样细胞(TIM)亚群的变化,这些变化可能会损害抗肿瘤T细胞免疫。因此,配对单细胞分析提供了有关肿瘤驱动免疫变化的宝贵知识,为合理设计免疫治疗提供了有力工具。视频摘要。

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