Tumor Microenvironment: Key Players in Triple Negative Breast Cancer Immunomodulation

Abstract

Triple negative breast cancer (TNBC) is a heterogeneous disease and is highly related to immunomodulation. As we know, the most effective approach to treat TNBC so far is still chemotherapy. Chemotherapy can induce immunogenic cell death, release of damage-associated molecular patterns (DAMPs), and tumor microenvironment (TME) remodeling; therefore, it will be interesting to investigate the relationship between chemotherapy-induced TME changes and TNBC immunomodulation. In this review, we focus on the immunosuppressive and immunoreactive role of TME in TNBC immunomodulation and the contribution of TME constituents to TNBC subtype classification. Further, we also discuss the role of chemotherapy-induced TME remodeling in modulating TNBC immune response and tumor progression with emphasis on DAMPs-associated molecules including high mobility group box1 (HMGB1), exosomes, and sphingosine-1-phosphate receptor 1 (S1PR1), which may provide us with new clues to explore effective combined treatment options for TNBC.

Identification of a Lipid Metabolism-Associated Gene Signature Predicting Survival in Breast Cancer

“…CD8+T cells are the main kind of cytolytic lymphocytes in tumor microenvironment, while NK cells, a type of cytotoxic lymphocytes, are crucial constituents of the innate immune system and play a key role in immune surveillance. 22 This phenomenon may indicate that CD8+T cells and NK cells have the ability to target and kill tumor cells, consistent with previous studies, 24–28 which may be the reason why the low-risk group has a better prognosis than the high-risk group. Tumor infiltrating lymphocytes (TILs) can recognize and kill malignant tumor cells and are important endogenous inhibitors of tumor growth.…”

“…During BC progression, tumor immune microenvironment remodeling with the change of the ratio of immune cells and release of multiple immune inhibitory and reactive cytokines is a critical feature. 20 , 21 The role of the tumor microenvironment (TME) in breast cancer immunomodulation is vitally important, 22 and a better understanding of the immune cell infiltrate in the breast cancer microenvironment is crucial for the development of more effective therapeutic approaches. 23 By analyzing the pathways and functions of genes enriched in differences between the high- and low-risk groups, we observed a strong correlation between gene signature and immune function.…”

Hyaluronan Functions in Wound Repair That Are Captured to Fuel Breast Cancer Progression

“…These tissue damage-induced HA oligomers provide pro-inflammatory (e.g., support M1 macrophage polarization), proliferation and migration signals [5,28,29] (Figure 1), and are critical for initiating a response to injury. It is intriguing that DAMPs released in response to tumor cell death, are also implicated in breast cancer progression [30], providing another example of the similarities between wounds and breast tumors. and activate cellular signaling cascades; and hyaluronidases, which break the native HA polymer into fragments that differ from the native polymer in their signaling functions [5].…”

Cancer Immunology and Immunotherapies: Mechanisms That Affect Antitumor Immune Response and Treatment Resistance

“…Based on these factors, significant attention has been directed towards the recent advances in cancer immunology [ 5 , 6 , 7 , 8 , 9 , 10 ]. In the past decades, the discovery of Programmed cell death protein 1 (PD-1) and the Cytotoxic T-lymphocyte–associated antigen 4 (CTLA-4) has helped to develop immune checkpoint blockade therapies.…”

“…The review article by Mehdi et al [ 7 ] focuses on the role of methylation in manipulating cancer immunity. In addition to these general cancer immunology topics, reviews by Krishnamurthy et al [ 8 ], Zheng et al [ 9 ], and Marseglia et al [ 10 ] summarize immune regulation in specific cancer types, such as hepatocellular carcinoma, triple-negative breast cancer, and uveal melanoma.…”