Ferroptosis in TNBC: interplay with tumor-infiltrating immune cells and therapeutic implications.

Abstract

Triple-negative breast cancer (TNBC) is an aggressive subtype of breast cancer with limited treatment options and a poor prognosis. Immunotherapy has emerged as a promising approach for TNBC, with tumor-infiltrating immune cells (TICs) in the tumor microenvironment (TME) serving as a critical cellular basis for its efficacy. However, the success of immunotherapy in TNBC is often limited due to the immunosuppressive nature of the TME and the heterogeneity of TNBC. Ferroptosis, a form of iron-dependent programmed cell death regulated by metabolic networks including iron, glutathione (GSH), and lipid metabolism, has shown potential to enhance anti-tumor immunity. Recent studies have demonstrated that ferroptosis can modulate immune responses by promoting the infiltration and activation of TICs, thereby improving the outcomes of immunotherapy. However, ferroptosis in immunosuppressive cells such as regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) can trigger an "immunosuppressive wave," affecting other immune cells in the tumor immune microenvironment. This demonstrates the dual role of ferroptosis in TNBC therapy, emphasizing the need for a nuanced understanding of its effects on different immune cells and tumor cells. Herein, we further elaborate the role of ferroptosis in TNBC cells and its interactions with tumor-infiltrating immune cells (TICs) within the TME.