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

被引:927
作者
Lavin, Yonit [1 ,2 ,3 ]
Kobayashi, Soma [1 ,2 ,3 ]
Leader, Andrew [1 ,2 ,3 ]
Amir, El-ad David [2 ,3 ,9 ]
Elefant, Naama [10 ]
Bigenwald, Camille [1 ,2 ,3 ]
Remark, Romain [1 ,2 ,3 ,13 ]
Sweeney, Robert [6 ,7 ]
Becker, Christian D. [4 ]
Levine, Jacob H. [11 ]
Meinhof, Klaus [4 ]
Chow, Andrew [1 ,2 ,3 ]
Kim-Shulze, Seunghee [2 ,3 ,9 ]
Wolf, Andrea [6 ]
Medaglia, Chiara [10 ]
Li, Hanjie [10 ]
Rytlewski, Julie A. [12 ]
Emerson, Ryan O. [12 ]
Solovyov, Alexander [1 ,3 ,5 ,8 ]
Greenbaum, Benjamin D. [1 ,3 ,5 ,8 ]
Sanders, Catherine [12 ]
Vignali, Marissa [12 ]
Beasley, Mary Beth [8 ]
Flores, Raja [6 ]
Gnjatic, Sacha [2 ,3 ,5 ,9 ]
Pe'er, Dana [11 ]
Rahman, Adeeb [2 ,3 ,7 ,9 ]
Amit, Ido [10 ]
Merad, Miriam [1 ,2 ,3 ,9 ]
机构
[1] Icahn Sch Med Mt Sinai, Dept Oncol Sci, New York, NY 10029 USA
[2] Icahn Sch Med Mt Sinai, Precis Immunol Inst, New York, NY 10029 USA
[3] Icahn Sch Med Mt Sinai, Tisch Canc Inst, New York, NY 10029 USA
[4] Icahn Sch Med Mt Sinai, Div Pulmonol, New York, NY 10029 USA
[5] Icahn Sch Med Mt Sinai, Div Hematol Oncol, New York, NY 10029 USA
[6] Icahn Sch Med Mt Sinai, Dept Thorac Surg, New York, NY 10029 USA
[7] Icahn Sch Med Mt Sinai, Dept Genet & Genom Sci, New York, NY 10029 USA
[8] Icahn Sch Med Mt Sinai, Dept Pathol, New York, NY 10029 USA
[9] Icahn Sch Med Mt Sinai, Human Immune Monitoring Ctr, New York, NY 10029 USA
[10] Weizmann Inst Sci, Dept Immunol, IL-76100 Rehovot, Israel
[11] Sloan Kettering Inst, Computat & Syst Biol Program, New York, NY 10065 USA
[12] Adapt Biotechnol Inc, Seattle, WA 98102 USA
[13] Innate Pharma, 117 Ave Luminy, F-13009 Marseille, France
关键词
TERTIARY LYMPHOID STRUCTURES; FLOW-CYTOMETRIC ANALYSIS; DENDRITIC CELLS; MYELOID CELLS; GENE-EXPRESSION; T-CELLS; RNA-SEQ; CANCER; MACROPHAGES; MONOCYTES;
D O I
10.1016/j.cell.2017.04.014
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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, noninvolved 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.
引用
收藏
页码:750 / 765
页数:16
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