Origin and Role of a Subset of Tumor-Associated Neutrophils with Antigen-Presenting Cell Features in Early-Stage Human Lung Cancer

Cancer Cell. 2016 Jul 11;30(1):120-135. doi: 10.1016/j.ccell.2016.06.001. Epub 2016 Jun 30.


Based on studies in mouse tumor models, granulocytes appear to play a tumor-promoting role. However, there are limited data about the phenotype and function of tumor-associated neutrophils (TANs) in humans. Here, we identify a subset of TANs that exhibited characteristics of both neutrophils and antigen-presenting cells (APCs) in early-stage human lung cancer. These APC-like "hybrid neutrophils," which originate from CD11b(+)CD15(hi)CD10(-)CD16(low) immature progenitors, are able to cross-present antigens, as well as trigger and augment anti-tumor T cell responses. Interferon-γ and granulocyte-macrophage colony-stimulating factor are requisite factors in the tumor that, working through the Ikaros transcription factor, synergistically exert their APC-promoting effects on the progenitors. Overall, these data demonstrate the existence of a specialized TAN subset with anti-tumor capabilities in human cancer.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Antigen-Presenting Cells / immunology*
  • Gene Expression Regulation, Neoplastic
  • Granulocyte-Macrophage Colony-Stimulating Factor / immunology
  • Humans
  • Ikaros Transcription Factor / metabolism
  • Interferon-gamma / immunology
  • Lung Neoplasms / immunology*
  • Neoplasm Staging
  • Neutrophils / cytology
  • Neutrophils / immunology*
  • T-Lymphocytes, Cytotoxic / immunology


  • Ikaros Transcription Factor
  • Interferon-gamma
  • Granulocyte-Macrophage Colony-Stimulating Factor