Research advances in the interplay between ferroptosis and T cells in the tumor microenvironment (Review)

Despite advances in tumor immunotherapy, its clinical efficacy remains constrained by challenges such as limited response rates, drug resistance and an immunosuppressive microenvironment; moreover, conventional therapeutic strategies often overlook the key constraints imposed by intrinsic tumor cell death resistance and metabolic reprogramming on antitumor immune responses. Based on the aforementioned practical dilemmas, the present review focused on the reciprocal regulatory crosstalk between ferroptosis and T cell immunity within the tumor microenvironment (TME) and further proposes novel therapeutic strategies that co‑target ferroptosis in tumor cells and T cell immunity. Ferroptosis substantially strengthens T cell‑dependent antitumor immunity. In turn, activated T cells dynamically regulate the susceptibility of tumor cells to ferroptosis, forming a positive immune feedback loop. Related combinatorial strategies have shown synergistic potential in preclinical studies, opening promising avenues to overcome existing therapeutic resistance. Nevertheless, multiple barriers impede clinical translation, including tumor heterogeneity, off‑target toxicity of ferroptosis inducers and dysregulation of T cell subset balance. To address these issues, future application of nanodelivery systems for TME‑specific intervention, combined with differential metabolic remodeling to reshape immunosuppressive networks, is expected to drive the development of next‑generation precision immunotherapeutic combinations. Collectively, the present review systematically elucidated the mechanistic interplay between ferroptosis and T cell immunometabolism, providing a theoretical foundation for developing targeted therapies to overcome tumor immune resistance.