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

• Published in: Cell Vol. 169; no. 4; pp. 750 - 765.e17
• Main Authors: Lavin, Yonit, Kobayashi, Soma, Leader, Andrew, Amir, El-ad David, Elefant, Naama, Bigenwald, Camille, Remark, Romain, Sweeney, Robert, Becker, Christian D., Levine, Jacob H., Meinhof, Klaus, Chow, Andrew, Kim-Shulze, Seunghee, Wolf, Andrea, Medaglia, Chiara, Li, Hanjie, Rytlewski, Julie A., Emerson, Ryan O., Solovyov, Alexander, Greenbaum, Benjamin D., Sanders, Catherine, Vignali, Marissa, Beasley, Mary Beth, Flores, Raja, Gnjatic, Sacha, Pe’er, Dana, Rahman, Adeeb, Amit, Ido, Merad, Miriam
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 04.05.2017
• Subjects: adenocarcinoma; Adenocarcinoma - immunology; Adenocarcinoma - pathology; Adenocarcinoma of Lung; barcoding; CD141+ DC; CD1c+ DC; Dendritic Cells - pathology; human non-small cell lung cancer (NSCLC); Humans; immune cell atlas; immunity; Immunity, Innate; immunotherapy; Killer Cells, Natural - pathology; lung adenocarcinoma; lung neoplasms; Lung Neoplasms - immunology; Lung Neoplasms - pathology; Macrophages - pathology; NK Cell; patients; Single-Cell Analysis - methods; T Cell; T-lymphocytes; T-Lymphocytes - pathology; TIM; TLS; tumor macrophage; Tumor Microenvironment; NK Cell; immune cell atlas; human non-small cell lung cancer (NSCLC); T Cell; lung adenocarcinoma; TIM; TLS; CD1c+ DC; CD141+ DC; tumor macrophage
• ISSN: 0092-8674; 1097-4172; 1097-4172
• DOI: 10.1016/j.cell.2017.04.014

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. [Display omitted] [Display omitted] •Paired analysis reveals a unique tumor-immune signature independent of TNM stage•Depletion of CD141+ DC and enrichment of PPARγhi macrophages in early stage lung cancer•Reduced and impaired NK cells in early stage lung cancer•Harnessing TIM compartment may help enhance T cell immunotherapies Comparing single tumor cells with adjacent normal tissue and blood from patients with lung adenocarcinoma charts early changes in tumor immunity and provides insights to guide immunotherapy design.