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

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

Author information

1
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.
2
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.
3
Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.
4
Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Genetics and Genomic Sciences, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
5
Division of Pulmonology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
6
Computational and Systems Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
7
Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
8
Adaptive Biotechnologies Inc., Seattle, WA 98102, USA.
9
Department of Oncological Sciences, 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; Division of Hematology/Oncology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA; Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
10
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
11
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; Division of Hematology/Oncology, 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.
12
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; Department of Genetics and Genomic Sciences, 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.
13
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; Human Immune Monitoring Center, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA. Electronic address: miriam.merad@mssm.edu.

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.

KEYWORDS:

CD141+ DC; CD1c+ DC; NK Cell; T Cell; TIM; TLS; human non-small cell lung cancer (NSCLC); immune cell atlas; lung adenocarcinoma; tumor macrophage

PMID:
28475900
PMCID:
PMC5737939
DOI:
10.1016/j.cell.2017.04.014
[Indexed for MEDLINE]
Free PMC Article

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