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. GreenbaumCatherine Sanders, Marissa Vignali, Mary Beth Beasley, Raja Flores, Sacha Gnjatic, Dana Pe'er, Adeeb Rahman, Ido Amit, Miriam Merad

Research output: Contribution to journalArticlepeer-review

861 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)750-765.e17
JournalCell
Volume169
Issue number4
DOIs
Publication statusPublished - 4 May 2017
Externally publishedYes

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

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