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PMID: 28475900 Published · ppublish English Journal Article

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

Cell ·Vol. 169 ·No. 4 ·2017-00-04 ·Pages 750-765.e17

Lavin Y, Kobayashi S, Leader A, Amir ED, Elefant N, Bigenwald C, Remark R, Sweeney R, Becker CD, Levine JH, Meinhof K, Chow A, Kim-Shulze S, Wolf A, Medaglia C, Li H, Rytlewski JA, Emerson RO, Solovyov A, Greenbaum BD, Sanders C, Vignali M, Beasley MB, Flores R, Gnjatic S, Pe'er D, Rahman A, Amit I, Merad M

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,pathology Adenocarcinoma of Lung Dendritic Cells/pathology Humans Immunity, Innate Killer Cells, Natural/pathology Lung Neoplasms/immunology,pathology Macrophages/pathology Single-Cell Analysis/methods T-Lymphocytes/pathology Tumor Microenvironment
Authors & Affiliations
29 authors, click to expand affiliations / ORCID
Lavin Yonit
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.
Kobayashi Soma
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.
Leader Andrew
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.
Amir El-Ad David
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.
Elefant Naama
Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.
Bigenwald Camille
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.
Remark Romain
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.
Sweeney Robert
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.
Becker Christian D
Division of Pulmonology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Levine Jacob H
Computational and Systems Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
Meinhof Klaus
Division of Pulmonology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Chow Andrew
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.
Kim-Shulze Seunghee
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.
Wolf Andrea
Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Medaglia Chiara
Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.
Li Hanjie
Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.
Rytlewski Julie A
Adaptive Biotechnologies Inc., Seattle, WA 98102, USA.
Emerson Ryan O
Adaptive Biotechnologies Inc., Seattle, WA 98102, USA.
Solovyov Alexander
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.
Greenbaum Benjamin D
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.
Sanders Catherine
Adaptive Biotechnologies Inc., Seattle, WA 98102, USA.
Vignali Marissa
Adaptive Biotechnologies Inc., Seattle, WA 98102, USA.
Beasley Mary Beth
Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Flores Raja
Department of Thoracic Surgery, Icahn School of Medicine at Mount Sinai, New York, NY 10029, USA.
Gnjatic Sacha
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.
Pe'er Dana
Computational and Systems Biology Program, Sloan Kettering Institute, New York, NY 10065, USA.
Rahman Adeeb
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.
Amit Ido
Department of Immunology, Weizmann Institute, Rehovot 76100, Israel.
Merad Miriam
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.
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Article Info
Journal
Cell
Abbr.
Cell
ISSN
1097-4172
DOI
10.1016/j.cell.2017.04.014
Email
miriam.merad@mssm.edu
Published
2017-00-04
Pages
750-765.e17
Language
English
Region
United States
NLM ID
0413066
PMCID
PMC5737939
Subset
IM
Grants
NCI NIH HHS · R01 CA164729 · United States
NCI NIH HHS · R01 CA154947 · United States
NCI NIH HHS · R01 CA190400 · United States
NICHD NIH HHS · DP1 HD084071 · United States
NIGMS NIH HHS · T32 GM008798 · United States
NCI NIH HHS · R01 CA173861 · United States
NIAID NIH HHS · U24 AI118644 · United States
NIAID NIH HHS · U19 AI128949 · United States
NIAID NIH HHS · U19 AI117873 · United States
Corrections
CommentIn
PMID: 28475889
CommentIn
PMID: 28492266
CommentIn
PMID: 28548134
CommentIn
PMID: 28602618
CommentIn
PMID: 28684257
External Links
PubMed source DOI: 10.1016/j.cell.2017.04.014 PMC Full Text View journal details
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