Ferroptosis and immunotherapy: Breaking barriers in cancer treatment resistance. (2025)

Cancer treatment has been revolutionized by immunotherapy; however, its efficacy is often hindered by intrinsic or acquired resistance mechanisms within the tumor microenvironment. Ferroptosis, a regulated form of cell death driven by iron-dependent lipid peroxidation, has recently emerged as a potent strategy to overcome these therapeutic barriers. This review explores the dynamic interplay between ferroptosis and immune responses, highlighting how ferroptosis modulates macrophage polarization, T cell activity, and cytokine signaling to reshape the immunosuppressive tumor milieu. The induction of ferroptosis enhances tumor immunogenicity, facilitates T cell infiltration, and sensitizes resistant cancer cells to immune checkpoint inhibitors, CAR T-cell therapy, and monoclonal antibodies. A