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BY  \nShensi Shen,  \nSichuan University, China  \nREVIEWED BY  \nAnkita Leekha,  \nUniversity of Houston, United States Qiming Gong,  \nSouthwest Medical University, China  \n*CORRESPONDENCE Liancheng Zhu  \n [zhulc@cmu.edu.cn](zhulc@cmu.edu.cn)  \nRECEIVED 31 March 2024  \nACCEPTED 24 July 2024  \nPUBLISHED 13 August 2024  \nCITATION  \nGuo K, Lu M, Bi J, Yao T, Gao J, Ren F and Zhu L (2024) Ferroptosis: mechanism, immunotherapy and role in ovarian cancer. Front. Immunol. 15:1410018 .  \ndoi: 10.3389/fimmu.2024.1410018  \nCOPYRIGHT  \n© 2024 Guo, Lu, Bi, Yao, Gao, Ren and Zhu. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY) . The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.  \nFerroptosis: mechanism, immunotherapy and role in ovarian cancer  \nKe Guo 1, Miao Lu 1, Jianlei Bi 2, Tianyu Yao 1, Jian Gao 1, Fang Ren 1 and Liancheng Zhu 1*  \n1 Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, Liaoning, China, 2 Department of Obstetrics and Gynecology, The Second Hospital of Dalian Medical University, Dalian, Liaoning, China  \nOvarian cancer is currently the second most common malignant tumor among gynecological cancers worldwide, primarily due to challenges in early diagnosis, high recurrence rates, and resistance to existing treatments. Current therapeutic options are inadequate for addressing the needs of ovarian cancer patients. Ferroptosis, a novel form of regulated cell death with demonstrated tumorsuppressive properties, has gained increasing attention in ovarian malignancy research. A growing body of evidence suggests that ferroptosis plays a significant role in the onset, progression, and incidence of ovarian cancer. Additionally, it has been found that immunotherapy, an emerging frontier in tumor treatment, synergizes with ferroptosis in the context of ovarian cancer. Consequently, ferroptosis is likely to become a critical target in the treatment of ovarian cancer.  \nKEYWORDS  \nferroptosis, ovarian cancer, Xc system, MDSC, immunotherapy  \n1 Introduction  \nOvarian cancer is one of the most prevalent and deadly subtypes of gynecological malignant tumors. There are several types of ovarian cancer, with epithelial ovarian cancer being the most common (1) . Ovarian cancer is typically diagnosed using a combination of therapies, including surgery, chemotherapy, and innovative immunotherapy. Between 1976 and 2015, the death rate from ovarian cancer in the United States declined by 33%, while its incidence fell by 29% between 1985 and 2014 (2) . However, the five-year survival rate of patients remained less than thirty percent (2), leading to a higher mortality rate among female reproductive system malignancies, as the majority of ovarian cancers were only discovered in stage III (51%) or stage IV (29%) (3) . Furthermore, there is a lack of treatment resistance and early diagnostic targets for ovarian cancer. Therefore, novel therapeutics are urgently needed to improve the early diagnosis, treatment, and prognosis of ovarian cancer.  \nFrontiers in Immunology 01 [frontiersin.org](frontiersin.org)  \nFerroptosis is a novel process of iron-dependent regulated cell death induced by erastin, characterized by the accumulation of iron ions, increased lipid peroxide concentration, reduced glutathione peroxidase 4 (GPx4) activity, and often accompanied by large amounts of reactive oxygen species (4) . Ferroptosis has been shown to be intimately associated with several biological processes and diseases, including Alzheimer’s disease and brain hemorrhage. Furthermore, it ha","cbCainmRAzEtyRS7","https://ap.wps.com/l/cbCainmRAzEtyRS7","pdf",1456571,16,"English","# Introduction\n## Mechanism of ferroptosis\n### GPX4-GSH pathway","[{\"question\":\"Why is ovarian cancer difficult to treat effectively?\",\"answer\":\"Ovarian cancer has challenges in early diagnosis, high recurrence rates, and resistance to current treatments, resulting in poor outcomes.\"},{\"question\":\"What is ferroptosis and what characterizes it?\",\"answer\":\"Ferroptosis is an iron-dependent regulated cell death marked by iron accumulation, increased lipid peroxides, reduced GPX4 activity, and often elevated reactive oxygen species.\"},{\"question\":\"How do immunotherapy and ferroptosis relate in ovarian cancer?\",\"answer\":\"Immunotherapy is suggested to synergize with ferroptosis in ovarian cancer, making ferroptosis a promising critical target for future treatment strategies.\"}]","Ferroptosis: mechanism, immunotherapy and role in ovarian cancer | PDF",1789997873]