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

通过配对单细胞分析揭示早期肺腺癌的先天免疫图谱

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

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 .

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