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

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

doi:10.1016/j.cell.2017.04.014

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

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

Authors

Yonit Lavin¹, Soma Kobayashi¹, Andrew Leader¹, El-Ad David Amir², Naama Elefant³, Camille Bigenwald¹, Romain Remark¹, Robert Sweeney⁴, Christian D Becker⁵, Jacob H Levine⁶, Klaus Meinhof⁵, Andrew Chow¹, Seunghee Kim-Shulze², Andrea Wolf⁷, Chiara Medaglia³, Hanjie Li³, Julie A Rytlewski⁸, Ryan O Emerson⁸, Alexander Solovyov⁹, Benjamin D Greenbaum⁹, Catherine Sanders⁸, Marissa Vignali⁸, Mary Beth Beasley¹⁰, Raja Flores⁷, Sacha Gnjatic¹¹, Dana Pe'er⁶, Adeeb Rahman¹², Ido Amit³, Miriam Merad¹³

Affiliations

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.

MeSH terms

Adenocarcinoma / immunology*
Adenocarcinoma / pathology*
Adenocarcinoma of Lung
Dendritic Cells / pathology
Humans
Immunity, Innate*
Killer Cells, Natural / pathology
Lung Neoplasms / immunology*
Lung Neoplasms / pathology*
Macrophages / pathology
Single-Cell Analysis / methods*
T-Lymphocytes / pathology
Tumor Microenvironment

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

Authors

Affiliations

Abstract

MeSH terms

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