Fig. 10

Overview of the relationship between SAT1 and ferroptosis, immune checkpoint blockade and chemoradiotherapy. IDH mutation results in abnormal 2-HG production, which remarkablely suppresses a-KG function, and thus irritate ferroptosis. P53 can promote ferroptosis by enhancing SAT1 which increases the expression of ALOX15. The increased expression of SAT1 was related to the resistance of tumor cells to radiotherapy. The TMZ-driven mechanisms of cell death are dependent of ferroptosis and autophagy in tumor cells. The activation of the autophagy pathway contributes to ferroptosis through the degradation of ferritin. SAT1 is expressed on immune cells and has a strong correlation with CD8 + T cells and its corresponding markers CD8A and CD8B. The immune checkpoint blockade activates CD8 + T cells and potentiates IFNγ signaling pathway to inhibit system xc- expression which leads to induce tumor cell ferroptosis. Tumor-infiltrating cytotoxic T cells expressed the inhibitory NK-cell receptor CD161. Blocking the inhibitory CD161–CLEC2D pathway activated T cell–mediated killing of glioma cells