Cross-Talk of Breast Cancer Cells with the Immune System

Understanding the pathogenesis of breast and other cancers requires an improved understanding of the local microenvironment in which cancer develops and progresses (Hanahan and Weinberg, 2011). Many cell types have been defined as key components of the tumor stroma that contributes to tumor growth and metastasis, and modulates the response to treatment. In this chapter we will focus on cells of the immune system, critical players with dual function comprising cells that can foster a pro-tumorigenic inflammatory environment as well as reject tumors (Demaria et al., 2010). Importantly, the therapeutic manipulation of the host immune system has a tremendous potential to enhance the response of breast cancer patients to treatment. Therefore, it is imperative to understand the cross-talk between breast cancer cells and cells of the innate and adaptive immune system. Several cell communication systems are involved in this cross-talk, including proinflammatory and immunosuppressive cytokines, chemokines and endogenous danger signals, known as damage-associated molecular pattern (DAMP) molecules that bind to Toll-like Receptors (TLR). Some of these factors represent interesting targets for immunotherapy strategies based on their known ability to stimulate the immune system, but in the context of the tumor microenvironment these immune stimulatory agents may also produce unwanted pro-tumorigenic effects by binding to receptors ectopically expressed on the cancer cells. Others are involved in recruiting to the tumor immune cells with regulatory and immune suppressive functions that protect the tumor from immune rejection. Clearly, the cross-talk between epithelial cells and the immune system is distorted in cancer to promote tumor growth and progression. We will review pre-clinical and clinical data in support of the concept that the cross-talk between neoplastic and immune cells is a key determinant of tumor behavior and treatment outcomes. The mediators of this cross-talk that have been identified in breast cancer will be discussed. Ultimately, improved understanding of the potential double-edge sword quality of therapies targeting mediators of this cross-talk is essential for a cautious use of immune response modifiers to harness the positive (anti-tumor immune reactivity) without promoting the negative (tumor growth, immune suppression) effects.