Ferroptosis is an iron-dependent regulated cell death (RCD) triggered by lipid peroxidation and governed by oxidative and antioxidant systems, distinguishing it from necrosis, apoptosis, and autophagy in terms of cell morphology and function [1], [2]. Formally introduced by Dixon [3] in 2012, ferroptosis has garnered significant attention, with numerous studies exploring its biology, mechanisms, regulation, and roles in various diseases [4]. Recent evidence suggests that ferroptosis contributes to the development of various diseases, including tumors, neurological diseases, acute kidney injury, and ischemia/reperfusion injury [2]. Among these, tumors remain a major public health challenge with a rising incidence and limited effective treatment options [5], [6].

Ferroptosis is a viable strategy for treating tumors. Ferroptosis inducers (FINs), such as erastin (system xc- inhibition) [7], sulfasalazine (system xc- inhibition) [8], and RSL3 (glutathione peroxidase 4 (GPX4) inhibition) [9] have been identified before ferroptosis and have demonstrated efficacy in inhibiting tumor growth in experimental animal models. Notably, some FINs, including sulfasalazine, have been approved by U.S. Food & Drug Administration (FDA) for clinical use [10]. Additionally, certain herbal extracts and nanomaterials that target ferroptosis exhibit potent tumor cell-killing abilities [11], [12], [13]. The intricate transcriptional regulatory network of tumor cells influences the expression of intrinsic ferroptosis-regulated proteins, primarily governed by the transcription factors P53, NRF2, YAP, and TAZ [11]. Consequently, these transcription factors affect the sensitivity of tumor cells to ferroptosis. Another promising strategy involves combining ferroptosis with existing tumor therapies, such as radiotherapy and chemotherapy, which have been shown to induce ferroptosis, with FINs enhancing tumor sensitivity to these treatments [14], [15], [16]. Exploring the commonalities between tumor therapy and ferroptosis holds promise for the development of innovative strategies.

In cancer treatment, immunotherapy has revolutionized patient outcomes, leading to long-term remission and improved survival rates over the past decade [17]. Increasing evidence suggests that ferroptosis plays an important role in immunotherapy [18], [19], [20]. Although the identification of ferroptosis as a form of immunogenic cell death (ICD) remains controversial [21], the connection between ferroptosis and tumor immunity has been strengthened by a compelling demonstration that CD8+ T cells can induce ferroptosis in tumor cells [22]. The inherent immunogenicity of ferroptosis, coupled with its interaction with immune cells is a potential breakthrough in overcoming the limitations of tumor immunotherapy. Consequently, this review aimed to investigate the critical regulatory mechanisms governing ferroptosis and provide an overview of the immunogenic characteristics of ferroptotic tumor cells. Additionally, we explored the implications of ferroptosis on anti-tumor immunity, translating novel insights into strategies for integrating ferroptosis with immunotherapy.