Understanding the Role of Innate Immune Cells and Identifying Genes in Breast Cancer Microenvironment

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.

Characterization of Gene Expression Signatures for the Identification of Cellular Heterogeneity in the Developing Mammary Gland

“…S9D). Interestingly, B-cell populations clustered closely with Natural Killer (NK) cells (mNEC12), cells known for playing an important role during mammary gland involution and breast tumorigenesis [82,83], and that are defined by genes like Killer Cell Lectin Like Receptor K1 (Klrk1) [84], Killer Cell Lectin Like Receptor D1 (Klrd1) [85], and Sialic acid binding Ig-like lectin H (Siglech) [86] (Fig. 4C, and Supplementary Fig.…”

Targeting Innate Immunity in Breast Cancer Therapy: A Narrative Review

“…To understand the breast tumor microenvironment, preclinical studies have been shown that innate immune cells and the secreted cytokines have multifaceted roles that either promote or suppress breast tumor during disease progression or therapeutic responses. For instance, when upon interaction with tumor antigen via TLR or STING that primarily expressed on DCs and macrophages, these stimulated 46). This also leads to another opportunity of developing routine immunoprofiling analysis of breast tumors and patients, which should be matched to effective strategy during treatment planning and prognosis.…”

“…The secreted IL-12 and type I IFNs also can activate NK cells for lysing tumor cells. Meanwhile, breast tumor cells synthesize and secret TGFβ that directly or indirectly target various immune cells, which altogether mediate the immune escape for invasion and metastasis ( 46 ). This also leads to another opportunity of developing routine immunoprofiling analysis of breast tumors and patients, which should be matched to effective strategy during treatment planning and prognosis.…”

“…Innate immunity is the primary defense line of the host against mammary tumor progression. Upon encountering dying breast tumor cells released components, immune surveillance is established for direct antitumor activities, including immune recognition and suppression ( 46 , 47 ). Specifically, the anticancer innate immune cells participate in releasing cytotoxic contents to directly kill target breast tumor cells, engaging professional antigen-presenting cells to detect and remove breast tumor cells, and further activating the phagocytosis process or alternative complement pathways.…”

Nanoparticles Targeting Innate Immune Cells in Tumor Microenvironment

“…The innate immune system originally serves as an initial border of defense against foreign invaders and alerts the adaptive immune system of impending attacks [ 7 ]. In TME, a large number of innate immune cells indirectly influences tumor progression by controlling T-cell functions [ 8 , 9 ]. For example, type-2 (M2) TAMs express multiple immunosuppressive and tumor promoting factors, such as prostaglandin E2, vesicular endothelial growth factor, and IL-10, leading to suppressed anti-tumor responses [ 10 ].…”