Abstract
The innate immune system is the first line of defense against invading pathogens and has a major role in clearing transformed cells, besides its essential role in activating the adaptive immune system. Macrophages, dendritic cells, NK cells, and granulocytes are part of the innate immune system that accumulate in the tumor microenvironment such as breast cancer. These cells induce inflammation in situ by secreting cytokines and chemokines that promote tumor growth and progression, in addition to orchestrating the activities of other immune cells. In breast cancer microenvironment, innate immune cells are skewed towards immunosuppression that may lead to tumor evasion. However, the mechanisms by which immune cells could interact with breast cancer cells are complex and not fully understood. Therefore, the importance of the mammary tumor microenvironment in the development, growth, and progression of cancer is widely recognized. With the advances of using bioinformatics and analyzing data from gene banks, several genes involved in NK cells of breast cancer individuals have been identified. In this review, we discuss the activities of certain genes involved in the cross-talk among NK cells and breast cancer. Consequently, altering tumor immune microenvironment can make breast tumors more responsive to immunotherapy.
Highlights
Innate immune cells present in the tumor microenvironment such as macrophages, myeloid-derived suppressive cells (MDSC), and neutrophils are associated with immunosuppression, poor prognosis, suppressive cells (MDSC), and neutrophils are associated with immunosuppression, poor prognosis, and tumor progression [31]
The role of neutrophils in breast cancer is still controversial and not clear. Despite their low frequency in the primary tumor microenvironment, neutrophils play a major role in the initiation of the metastasis of breast cancer, where their numbers increase as the metastasis progresses [104,105]
The protein encoded by ZAP70 gene is a very vital protein that is accompanied by immunoreceptor tyrosine activating motif (ITAM) that can be activated in natural killer (NK) cells [45]
Summary
Among all types of cancer, breast cancer is the most frequent type in women worldwide. The complete interaction between breast cancer cells and the immune cells in the tumor microenvironment is not very well understood [6,7]. Tumor cells may release some cellular components that may activate the innate immune cells, which in turn establish antitumor immunity in the microenvironment and induce tumor eradication [10,11]. Upon encounter with transformed tumor cells, some immune cells such as macrophages and dendritic cells become activated and release large amounts of pro-inflammatory cytokines such as IL-12, IL-15, and type 1 interferon (IFN) that activate natural killer (NK) cells and T helper cell differentiation [12,13]. The activation of innate cells in turn stimulates adaptive immune system by releasing large amounts of IFN-γ and chemokines including. Understanding the cross talk among these cell types and tumor cells can advance the knowledge of how immune cells infiltrate into the tumor microenvironment, which may help in choosing the best personalized immunotherapy therapeutic approaches
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