Current advances on the role of ferroptosis in tumor immune evasion

Abstract

Ferroptosis is a non-apoptotic form of regulated cell death characterized by iron accumulation and uncontrolled lipid peroxidation, leading to plasma membrane rupture and intracellular content release. Cancer immunotherapy, especially immune checkpoint inhibitors (ICIs) targeting PD-1 and PD-L1, has been considered a breakthrough in cancer treatment, achieving encouraging clinical anti-tumor effects in a variety of cancers. However, tumor immune evasion is indispensable to immunotherapy failure. The mechanisms of tumor immune evasion are quite complex, and its occurrence is inseparable from the ferroptosis in tumor microenvironment (TME). Thus, a comprehensive understanding of the role of ferroptosis in tumor immune evasion is crucial to enhance the efficacy of immunotherapy. In this review, we provide an overview of the recent advancements in understanding ferroptosis in cancer, covering molecular mechanisms and interactions with the TME. We also summarize the potential applications of ferroptosis induction in immunotherapy, as well as ferroptosis inhibition for cancer treatment in various conditions. We finally discuss ferroptosis as a double-edged sword, including the current challenges and future directions regarding its potential for cancer treatment.