The ferroptosis-ncRNA-exosome triad: key orchestrators in cancer immunopathogenesis

Ferroptosis is an iron-dependent lipid peroxidation-regulated cell death mechanism that serves a paradoxical role in cancer immunopathogenesis. The complex relationships between ferroptosis, exosomes, and non-coding RNAs (ncRNAs) have recently been identified as an attractive subject in the field of immune system regulation in cancer. Although ferroptosis activates immune responses by inducing the release of damage-associated molecular patterns (DAMPs), it can also result in immune tolerance via the release of immunosuppressive molecules, highlighting the dual role of ferroptosis in either immune activation or suppression. Exosomes function as key components of the tumor microenvironment for regulating ferroptosis and immune responses, in which they protect cancer cells from ferroptosis and contribute to immunosuppression and metabolic remodeling. lncRNAs regulate ferroptosis through modulating miRNAs; for instance, lncRNA PVT1 or exosomal-PVT1 has been shown to cause miR-214-3p-mediated GPX4 inhibition, inducing ferroptosis in hepatocellular cancer cells in vitro. In this regard, elucidating the precise correlation between ferroptosis, exosome dynamics, and lncRNA involved in cancer immunopathogenesis may reveal new therapeutic approaches to improve cancer treatment success. Combining ferroptosis regulation with immunotherapy shows promise for cancer treatment; however, additional studies are required to understand these mechanisms for developing innovative therapeutic approaches for cancer patients.