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Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells.

ABSTRACT: Epithelial-to-mesenchymal transition (EMT) is a process through which epithelial cells lose their epithelial characteristics and cell-cell contact, thus increasing their invasive potential. In addition to its well-known roles in embryonic development, wound healing, and regeneration, EMT plays an important role in tumor progression and metastatic invasion. In breast cancer, EMT both increases the migratory capacity and invasive potential of tumor cells, and initiates protumorigenic alterations in the tumor microenvironment (TME). In particular, recent evidence has linked increased expression of EMT markers such as TWIST1 and MMPs in breast tumors with increased immune infiltration in the TME. These immune cells then provide cues that promote immune evasion by tumor cells, which is associated with enhanced tumor progression and metastasis. In the current review, we will summarize the current knowledge of the role of EMT in the biology of different subtypes of breast cancer. We will further explore the correlation between genetic switches leading to EMT and EMT-induced alterations within the TME that drive tumor growth and metastasis, as well as their possible effect on therapeutic response in breast cancer.

SUBMITTER: Singh S

PROVIDER: S-EPMC6572359 | biostudies-literature | 2019 May

REPOSITORIES: biostudies-literature

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Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells.

Singh Snahlata S Chakrabarti Rumela R

Journal of clinical medicine 20190509 5

Epithelial-to-mesenchymal transition (EMT) is a process through which epithelial cells lose their epithelial characteristics and cell-cell contact, thus increasing their invasive potential. In addition to its well-known roles in embryonic development, wound healing, and regeneration, EMT plays an important role in tumor progression and metastatic invasion. In breast cancer, EMT both increases the migratory capacity and invasive potential of tumor cells, and initiates protumorigenic alterations i ...[more]

PMID: 31075939

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Project description:In 2020, newly diagnosed breast cancer (BC) cases surpassed that of lung cancer among women, making it the most common female cancer globally. In spite of recent increases in incidence rates, mortality due to BC has declined since 1989. These declines have been attributed to advancements in treatment modalities as well as increased mammography surveillance. Despite these advances, African American (AA) women are 40% more likely to die from BC than Caucasian women. Multifactorial etiology has been implicated in the disparity of BC mortality rates among AA women. As an example, AA women have a disproportionate incidence of triple negative breast cancer (TNBC), which has a poor prognosis and marginal treatment options. Increasingly, the tumor microenvironment (TME) has gained relevance as it relates to primary tumor progression, metastasis and treatment possibilities. The treatment outcomes or pathological complete response (pCR) in TNBC among AA women are affected by differences in TME. The TME of AA women exhibit several variances in acellular and cellular components associated with pro-tumorigenic effects. For example, increased levels of the adipocyte-related hormone, resistin, the pro-inflammatory cytokine, IL-6, and the CC chemokine, CCL2, within the TME of AA women gives rise to an increased density of M2 macrophages, also known as tumor-associated macrophages. Elevated levels of vascular endothelial growth factor in the TME of AA women increase the vascular density or vascularity, which facilitate aggressive tumor growth and metastasis. Furthermore, a pro-tumorigenic TME is supported by increased levels of the CXC chemokine, CXCL12 that results in the recruitment of regulatory T lymphocytes (Tregs ). Due to these and other differences in the TME of AA women, precision oncology can target specific aspects of the TME that may contribute to a poorer prognosis. In addition to the discrepancies in the TME, AA women face socio-economic barriers that limit their ability to access state-of-the-art, novel therapies against metastatic TNBC. In this review, we will provide a brief overview of the tumor immune microenvironment, immune-based treatment options for TNBC and their potential to decrease health disparities due to ethnicity.

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Dataset Information

Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells.

Publications

Consequences of EMT-Driven Changes in the Immune Microenvironment of Breast Cancer and Therapeutic Response of Cancer Cells.

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