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Moreover, due to its thiol p K a value of 8.9 (Table 1), which is substantially above the physiological pH of the cytosol, only 2.9% of GSH are present as reactive thiolate anion at pH 7.4 [135]
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IFN-γ secreted by anti-PD-L1 immunotherapy-activated CD8 + T cells markedly down-regulates SLC3A2 and SLC7A11 expression in tumor cells through the JAK1-STAT1 signaling pathway (SLC3A2 and SLC7A11 are the two subunits that constitute the cystine/glutamate antiporter, known as System Xc − ), resulting in reduced cysteine uptake, compromised GPX-4 function, altered mitochondrial activity, heightened lipid peroxidation, and ultimately ferroptosis induction [17, 25]
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