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Figure 2 The potential signal is the arachidonic acid (AA) oxidation product released by ferroptosis cells therefore, it has been hypothesized that lipoxygenases (LOXs) can not only induce the PUFAs production but also promote ferroptosis cells to release immune signals and regulate tumor immunity ( via activating transcription factor NRF2 ( Prostaglandin E2 (PGE2) is considered to be one of the important immunosuppressive factors and it can be released after most death cells ( via inhibiting the secretion of CCL5 and XCL1 by NK cells ( + T cell-mediated immune response ( Recent studies have confirmed that GPX4 activity is associated with chronic inflammation ( In addition to releasing lipid mediators, ferroptosis cells can also release HMGB1 in an autophagy-dependent manner ( + T cells cytotoxic immune response against glioma and induce immunological memory ( In addition to the above cytokines, there are other cytokines worth exploring ( Challenges of Ferroptosis in GIME The glioma immunosuppressive microenvironment (GIME) is the main reason for poor efficacy of immunotherapy in glioma (93, 94)

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doi: 10.1016/j.jamcollsurg.2015.12.006