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Stromal Fibroblasts and the Immune Microenvironment: Partners in Mammary Gland Biology and Pathology?

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Abstract

The microenvironment of a tumor has emerged recently as a critical contributor to the development of cancer. Within this environment, fibroblasts and immune cells are the cell lineages that seem to be active mediators of tumour development. The activated fibroblasts that are also present during wound healing and chronic inflammation have been studied extensively. Their activation leads to altered gene expression profiles that markedly increase growth factor and cytokine secretion, leading to major alterations in the immune cell microenvironment. To better understand normal tissue development, wound healing and the chronic inflammation that leads to cancer, we review here information available on the role of fibroblasts and immune cells in normal breast development and in cancer. We also discuss the immunogenicity of breast cancer compared to other cancers and the contribution of the immune microenvironment to the initiation, progression and metastasis of tumors. Also reviewed is the limited knowledge on the role of immune cells and fibroblasts in normal development and whether the risk of cancer increases when their control is not tightly regulated.

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Abbreviations

APC:

Antigen presenting cell

BPH:

Benign prostatic hyperplasia

CAF:

Cancer associated fibroblast

CCL2:

Monocyte chemoattractant protein 1

COPD:

Chronic obstructive pulmonary disease

CSF-1:

Colony stimulating factor 1

CTLA-4:

Cytotoxic T lymphocyte antigen 4

CXCL12:

Stromal derived factor 1

DC:

Dendritic cell

DCIS:

Ductal carcinoma in-situ

DTR:

Diphtheria toxin receptor

ECM:

Extracellular matrix

EFG:

Epidermal growth factor

FAP:

Fibroblast activated protein

FGF:

Fibroblast growth factor

FGFR:

Fibroblast growth factor receptor

GH:

Growth hormone

IDC:

Invasive ductal carcinoma

IFN-γ:

Interferon gamma

IFN- β:

Interferon beta

mAb:

Monoclonal antibody

MDSC:

Myeloid Derived suppressor cell

MHC:

Major histocompatibility complex

MMP:

Matrix metalloproteinase

NF:

Normal fibroblast

NK:

Natural killer cell

pDC:

Plasmacytoid dendritic cell

RA:

Rheumatoid arthritis

TAM:

Tumor associated macrophage

TEB:

Terminal end bud

TGF-β:

Transforming growth factor beta

TIMP:

Tissue inhibitor of matrix metalloproteinase

TNF-α:

Tumor necrosis factor alpha

Treg:

Regulatory T cell

VEGF:

Vascular endothelial growth factor

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Acknowledgments

We would like to thank Dr Nicole Haynes for critical discussions and assistance with this review. We would also like to thank the National Breast Cancer Foundation (NBCF) of Australia for supporting Robin Anderson and Kara Britt with NBCF fellowships. Ashleigh Unsworth is supported by an Australian Postgraduate Award.

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  1. Peter MacCallum Cancer Centre, 7 St Andrews Place East, Melbourne, 3002, Australia

    Ashleigh Unsworth, Robin Anderson & Kara Britt

  2. The Sir Peter MacCallum Department of Oncology, University of Melbourne, Parkville, Australia

    Ashleigh Unsworth, Robin Anderson & Kara Britt

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  1. Ashleigh Unsworth
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Unsworth, A., Anderson, R. & Britt, K. Stromal Fibroblasts and the Immune Microenvironment: Partners in Mammary Gland Biology and Pathology?. J Mammary Gland Biol Neoplasia 19, 169–182 (2014). https://doi.org/10.1007/s10911-014-9326-8

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