Harnessing the immune system for the treatment of breast cancer

Abstract

Abstract:Standard treatment options for breast cancer include surgery, chemotherapy, radiation, and targeted therapies, such as adjuvant hormonal therapy and monoclonal antibodies. Recently, the recognition that chronic inflammation in the tumor microenvironment promotes tumor growth and survival during different stages of breast cancer development has led to the development of novel immunotherapies. Several immunotherapeutic strategies have been studied both preclinically and clinically and already have been shown to enhance the efficacy of conventional treatment modalities. Therefore, therapies targeting the immune system may represent a promising next-generation approach for the treatment of breast cancers. This review will discuss recent findings that elucidate the roles of suppressive immune cells and proinflammatory cytokines and chemokines in the tumor-promoting microenvironment, and the most current immunotherapeutic strategies in breast cancer.

Role of the Tumor Microenvironment in Breast Cancer

“…Accordingly, high numbers of T reg are associated with a worse prognosis in breast cancer [51,52]. It is believed that the tumor itself recruits T reg through prostaglandin E2 secretion as well as TGF-β signaling, and suppresses the functions of effector cells through the secretion of IL-10 and TGF-β to create an immunosuppressive microenvironment [53,54]. This process is called immunoediting [55] and has recently been recognized as another hallmark of cancer [54,56].…”

“…It is believed that the tumor itself recruits T reg through prostaglandin E2 secretion as well as TGF-β signaling, and suppresses the functions of effector cells through the secretion of IL-10 and TGF-β to create an immunosuppressive microenvironment [53,54]. This process is called immunoediting [55] and has recently been recognized as another hallmark of cancer [54,56]. Conversely, infiltration by CD8+ effector T cells is associated with longer breast cancer-specific survival, independent of other prognostic factors such as tumor grade, lymph node stage, tumor size, vascular invasion and HER2 status [50].…”

“…Conversely, infiltration by CD8+ effector T cells is associated with longer breast cancer-specific survival, independent of other prognostic factors such as tumor grade, lymph node stage, tumor size, vascular invasion and HER2 status [50]. However, the effect of CD8+ cytotoxic T cells is regulated by the balance between co-stimulatory and co-inhibitory signals at so-called immune checkpoints [54,57]. Immune checkpoint molecules such as programmed death-1 (PD-1), cytotoxic T-lymphocyte antigen 4 or B- and T-lymphocyte attenuator inhibit T-cell function, thus preventing inappropriate immune reactions and limiting the extent and duration of immune responses.…”

Green tea polyphenols induce cell death in breast cancer MCF-7 cells through induction of cell cycle arrest and mitochondrial-mediated apoptosis

“…There is no permanent treatment for cancer. Many treatment options for cancer exist, the primary ones including surgery, chemotherapy, radiation therapy, and palliative care (Hortobagyi et al, 1988;Jiang, 2014). However, most of them have doubtful efficacy, safety risks, and other serious adverse effects.…”

Macrophage-produced IL-10 limits the chemotherapy efficacy in breast cancer

“…TAMs have been known to promote breast cancer progression and increase therapy resistance through mechanisms such as the enhancement of angiogenesis, tumor cell proliferation and invasiveness by producing growth factors such as vascular endothelial growth factor (VEGF), epidermal growth factor (EGF) and FGF2 (Jiang, 2014). However, improved efficacy of chemotherapy by the means of TAM depletion has been shown to be dependent on the enhanced anti-tumor activity of CD8 + T cells (DeNardo et al, 2011).…”