Key Factor Regulating Inflammatory Microenvironment, Metastasis, and Resistance in Breast Cancer: Interleukin-1 Signaling

Abstract

Breast cancer is one of the top-ranked cancers for incidence and mortality worldwide. The biggest challenges in breast cancer treatment are metastasis and drug resistance, for which work on molecular evaluation, mechanism studies, and screening of therapeutic targets is ongoing. Factors that lead to inflammatory infiltration and immune system suppression in the tumor microenvironment are potential therapeutic targets. Interleukin-1 is known as a proinflammatory and immunostimulatory cytokine, which plays important roles in inflammatory diseases. Recent studies have shown that interleukin-1 cytokines drive the formation and maintenance of an inflammatory/immunosuppressive microenvironment through complex intercellular signal crosstalk and tight intracellular signal transduction, which were found to be potentially involved in the mechanism of metastasis and drug resistance of breast cancer. Some preclinical and clinical treatments or interventions to block the interleukin-1/interleukin-1 receptor system and its up- and downstream signaling cascades have also been proven effective. This study provides an overview of IL-1-mediated signal communication in breast cancer and discusses the potential of IL-1 as a therapeutic target especially for metastatic breast cancer and combination therapy and current problems, aiming at enlightening new ideas in the study of inflammatory cytokines and immune networks in the tumor microenvironment.

Inflammatory Breast Cancer: The Cytokinome of Post-Mastectomy Wound Fluid Augments Proliferation, Invasion, and Stem Cell Markers

“…HER2 increased drug-resistance-related CSCs in HER2+ breast cancer patients, yet the blocking of IL-1α signaling improved chemotherapy efficacy when combined with cisplatin and paclitaxel. Such results reflect the importance of combined therapy in breast cancer patients due to the interference of cytokines with targeted therapy [ 39 ], as we previously showed [ 40 ].…”

Study on the mechanism of MDSC-platelets and their role in the breast cancer microenvironment

“…By blocking the mTOR/S6K1/Myc signaling pathway, Shuangshen granules inhibit the development of BMCs into MDSCs and decrease the number of CD11b+Ly6C + Ly6G + cells in BC lung metastases (Wei et al, 2021). In mice, immune function can be variably suppressed by depression and tumor growth, and the microenvironment of advanced 4T1 inflammatory BC may be crucial for its pathogenesis (Liu et al, 2021). By lowering CD8 + T lymphocyte apoptosis and tumor cell activity, enhancing immune monitoring capacity, and decreasing MDSC proliferation, a Shugan Jianpi formula was able to regulate the immune microenvironment and increase the survival time of tumor-bearing mice (Lu et al, 2017).…”

Epstein‑Barr virus as a promoter of tumorigenesis in the tumor microenvironment of breast cancer (Review)

“…As already mentioned, the molecular process mediated by IL-1 include the inflammatory reactions of organs and cells, immune responses and homeostatic regulation, which confirms its participation in oncogenesis, invasion, and metastasis through a perpetuating condition with chronic proinflammatory state. Due to the immense therapeutic potential attributed to it, IL-1 inhibition has been used in BC, where gevokizumab, bermekimab and nidanilimab antibodies stand out with promising results in metastatic BC ( 97 ).…”