Ferroptosis, a subtle talk between immune system and cancer cells: To be or not to be?

Ferroptosis, an established form of programmed cell death discovered in 2012, is characterized by an imbalance in iron metabolism, lipid metabolism, and antioxidant metabolism. Activated CD8 + T cells can trigger ferroptosis in tumor cells by releasing interferon-γ, which initiates the ferroptosis program. Despite the remarkable progress made in treating various tumors with immunotherapy, such as anti-PD1/PDL1, there are still significant challenges to overcome, including limited treatment options and drug resistance. In this review, we exam the potential biological significance of the ferroptosis phenotype using bioinformatics and review the latest advancements in understanding the mechanism of ferroptosis-mediated anti-tumor immunotherapy. Furthermore, we revisit the host immune system, immune microenvironment, ferroptotic defense system, metabolic reprogramming, and key genes that regulate the occurrence and resistance of ferroptosis of tumor cell. Additionally, several immune-combined ferroptosis treatment strategies were put forward to improve immunotherapy efficacy and to provide new insights into reversing anti-tumor immune drug resistance.