Ferroptosis and tumor immunity: In perspective of the major cell components in the tumor microenvironment

Ferroptosis is an iron-dependent form of cell death driven by lipid peroxidation, which is morphologically, biochemically, and genetically distinct from apoptosis, necrosis, and autophagy. Mounting studies on the essential role of ferroptosis have been published in the progression of solid tumors, metastasis, therapy, and therapy resistance. Studies showed that ferroptosis is a "double-edged sword" in tumor immunity, which means it may have both tumor-antagonizing and tumor-promoting functions. The tumor microenvironment (TME) comprises not only tumor cells but also surrounding immune cells, stromal cells, as well as noncellular components such as the extracellular matrix (ECM), cytokines, growth factors, and extracellular vesicles (EVs). In the complex and diverse condition in TME where tumor cells grow, changes in each constituent may impact tumor destiny differently. Recently, several studies have revealed the interaction between ferroptosis and different constituents in TME. Both tumor cells and nontumor cells have a dual role in tumor immunity and influence tumor progression through ferroptosis. Herein, this review aims at summarizing the role of ferroptosis in tumor immunity based on TME, focusing on the mechanisms of the interaction between the ferroptosis and the different constituents in TME, illuminating how ferroptosis plays its role in promoting or antagonizing tumors by acting with varying components in TME and proposing several questions in immunomodulatory effects of ferroptosis and ferroptosis-associated immunotherapy.