Inflammation, immunosuppressive microenvironment and breast cancer: opportunities for cancer prevention and therapy

Abstract

Breast cancer is the most commonly diagnosed malignancy and a leading cause of cancer-related death in women worldwide. It also exhibits pronounced racial disparities in terms of incidence and clinical outcomes. There has been a growing interest in research community to better understand the role of the microenvironment in cancer. Several lines of evidence have highlighted the significance of chronic inflammation at the local and/or systemic level in breast tumor pathobiology. Inflammation can influence breast cancer progression, metastasis and therapeutic outcome by establishing a tumor supportive immune microenvironment. These processes are mediated through a variety of cytokines and hormones that exert their biological actions either locally or distantly via systemic circulation. Targeting of immune and inflammatory pathways has met tremendous success in some cancers underscoring the importance of research to further our understanding of these systems in breast cancer. This knowledge can be helpful not only in the development of novel prevention and therapeutic strategies, but also help in better prediction of therapeutic responses in patients. This review summarizes some of the significant findings on the role of inflammation in breast cancer to gain collective molecular and mechanistic insights. We also discuss ongoing efforts and future outlook to exploit the existing knowledge for improved breast cancer management.

Keywords: Breast cancer (BC); immune suppression; inflammation; tumor microenvironment (TME).

Figure 1

Histological and molecular classification of breast cancer. Classification is based on architectural features, growth pattern and the genetic landscape of breast tumors. IDC, invasive ductal carcinoma.

Figure 2

Schematic representation of the components of the inflammatory tumor microenvironment. Tumor-derived soluble factors induce mobilization and reprogramming of immune cells and activation of stromal cells in the tumor-adjacent extracellular matrix. Cytokines and/or growth factors secreted by these immune or stromal cells further regulate the activity of recruited immune cells leading to the sustenance of tumor favoring inflammatory tumor microenvironment. IL, interleukin; TGF-β, transforming growth factor β; MCP-1, monocyte chemoattractant protein-1; CSF, colony stimulating factor; NK, natural killer; PAI-1, plasminogen activator inhibitor-1; Arg-1, arginase 1.

Figure 3

Contribution of inflammatory tumor microenvironment in breast cancer progression. Interaction between the cells in the tumor microenvironment leads to enhanced production of cytokines, growth factors, angiogenic factors and proteolytic enzymes that help in sustaining tumor growth, promoting angiogenesis, and tumor cell invasion and metastasis. IL, interleukin; TGF-β, transforming growth factor β; MMP, matrix metalloproteinase; GM-CSF, granulocyte-macrophage colony stimulating factor; MCP-1, monocyte chemoattractant protein-1; VEGF, vascular endothelial growth factor.