Innate Immune Cells in Breast Cancer – From Villains to Heroes?

Abstract

The innate immune system ensures effective protection against foreign pathogens and plays important roles in tissue remodeling. There are many types of innate immune cells, including monocytes, macrophages, dendritic cells, and granulocytes. Interestingly, these cells accumulate in most solid tumors, including those of the breast. There, they play a tumor-promoting role through secretion of growth and angiogenic factors, as well as immunosuppressive molecules. This is in strong contrast to the tumor-suppressing effects that innate immune cells exert in vitro upon proper activation. Therapeutic approaches have been developed with the aim of achieving similar suppressive activities in vivo. However, multiple factors in the tumor microenvironment, many of which are immunosuppressive, represent a major obstacle to effective treatment. Here, we discuss the potential of combating breast cancer through activation of the innate immune system, including possible strategies to enhance the success of immunotherapy.

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Abbreviations

BCG:

Bacillus Calmette-Guerin

CD:

cluster of differentiation

CSF-1:

colony stimulating factor-1

DC:

dendritic cell

EGF:

epidermal growth factor

FasL:

Fas ligand

FGF:

fibroblast growth factor

GM-CSF:

granulocyte macrophage colony stimulating factor

HER2:

human epidermal growth factor receptor 2

HMGB-1:

high mobility group box protein-1

HSP:

heat shock protein

IFN:

interferon

IL:

interleukin

LAIR:

leukocyte-associated immunoglobulin-like receptor

LPS:

lipopolysaccharide

MDSC:

myeloid derived suppressor cells

MMP:

matrix metalloproteinase

NK cell:

natural killer cell

NLR:

nucleotide-binding oligomerization domain (NOD)-containing protein like receptor

NO:

nitric oxide

PAMP:

pathogen associated molecular pattern

PDL1:

programmed cell death receptor ligand

ROS:

reactive oxygen species

SR/CR:

spontaneous regression/complete resistance

STAT:

signal transducer and activator of transcription

TAM:

tumor associated macrophage

TGF-β:

transforming growth factor-β

Th1 :

type I T helper cell

Th2 :

type II T helper cell

TLR:

toll-like receptor

TNF-α:

tumor necrosis factor-α

TRAIL:

TNF-related apoptosis-inducing ligand

Treg:

regulatory T cell

VEGF:

vascular endothelial growth factor

ZA:

zoledronic acid

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Acknowledgements

We thank Elizabeth Nakasone, Jae-Hyun Park, and Miriam Fein for help with the layout of the figures and comments on the manuscript.

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Correspondence to Mikala Egeblad.

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Acknowledgement of financial support

This work was supported by funds from the National Cancer Institute (U01-CA141451), the Starr Cancer Consortium, the Breast Cancer Alliance, Susan G. Komen for the Cure, Long Island 2 Day Walk to Fight Breast Cancer and the Manhasset Women’s Coalition Against Breast Cancer.

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Kees, T., Egeblad, M. Innate Immune Cells in Breast Cancer – From Villains to Heroes?. J Mammary Gland Biol Neoplasia 16, 189 (2011). https://doi.org/10.1007/s10911-011-9224-2

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Keywords

  • Innate immune cells
  • Immunotherapy
  • Macrophages
  • Tumor microenvironment
  • Tumor-suppressing immune activities