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Phenotype and function of tumor-associated neutrophils and their subsets in early-stage human lung cancer

  • Focussed Research Review
  • Published:
Cancer Immunology, Immunotherapy Aims and scope Submit manuscript

Abstract

Neutrophils accumulate in many types of human and murine tumors and represent a significant portion of tumor-infiltrating myeloid cells. Our current understanding of the role of neutrophils in tumor development has depended primarily on murine models of cancer. However, there are crucial species differences in the evolution of tumors, genetic diversity, immune and inflammatory responses, and intrinsic biology of neutrophils that might have a profound impact on the tumor development and function of neutrophils in mouse versus human tumors. To date, the majority of experimental approaches to study neutrophils in cancer patients have been limited to the examination of circulating blood neutrophils. The phenotype and function of tumor-associated neutrophils (TANs) in humans, particularly in the early stages of tumor development, have not been extensively investigated. Thus, the long-term goal of our work has been to characterize human TANs and determine their specific role in tumor development. Here, we summarize our findings on human TANs obtained from human early stage lung cancer patients. We will describe the phenotypes of different TAN subsets identified in early stage lung tumors, as well as their functional dialog with T cells.

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Abbreviations

EGF:

Epidermal growth factor

FGF:

Fibroblast growth factors

G-MDSCs:

Granulocytic-myeloid-derived suppressor cells

HGF:

Hepatocyte growth factor

ICAM-1:

Intercellular adhesion molecule 1

LDN:

Low-density neutrophils

MCP-1:

Monocyte chemotactic protein 1

MPO:

Myeloperoxidase

NDN:

Normal density neutrophils

NSCLC:

Non-small cell lung carcinoma

NY-ESO-1:

New York-esophageal cancer-1

PBNs:

Peripheral blood neutrophils

PMN-MDSC:

Polymorphonuclear myeloid-derived suppressor cells

TANs:

Tumor-associated neutrophils

VEGF:

Vascular endothelial growth factor

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Acknowledgements

Thanks to Steven Albelda, Jason Stadanlick, Abhishek Rao, and Michael Annunziata for critical reading of this review. This work was supported by the Department of Defense (LC140199 # W81XWH-15-1-0717 to Evgeniy Eruslanov), National Institutes of Health (NIH)/National Cancer Institute (NCI) (RO1 CA187392-01A1 to Evgeniy Eruslanov), and the Lung Cancer Translation Center of Excellence of the Abramson Cancer Center at the University of Pennsylvania.

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  1. Division of Thoracic Surgery, Department of Surgery, Perelman School of Medicine, University of Pennsylvania, 3400 Spruce Street, 6 Silverstein, Philadelphia, PA, 19104, USA

    Evgeniy B. Eruslanov

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Correspondence to Evgeniy B. Eruslanov.

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This paper is a Focussed Research Review based on a presentation given at the conference Regulatory Myeloid Suppressor Cells: From Basic Discovery to Therapeutic Application which was hosted by the Wistar Institute in Philadelphia, PA, USA, 16th—19th June, 2016. It is part of a Cancer Immunology, Immunotherapy series of Focussed Research Reviews.

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Eruslanov, E.B. Phenotype and function of tumor-associated neutrophils and their subsets in early-stage human lung cancer. Cancer Immunol Immunother 66, 997–1006 (2017). https://doi.org/10.1007/s00262-017-1976-0

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