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The authors prove that the manganese (Mn 2+ ) treatment-induced tumor cell death is irrelevant to the apoptosis, necroptosis, pyroptosis or autophagy, but only to ferroptosis, in which type I interferons (IFNs) were the main mediators of downregulated DHODH expression and subsequent mitochondrial ROS accumulation

This represents a milestone in immuno-oncology, successfully leading to standard clinical guideline updates, which established immunotherapy as a component of curative-intent treatment for early-stage disease

Conclusion and Perspective Reactive oxygen species is not only a by-product of cellular metabolic programs but also a key signaling molecule involved in directing T cell activation and differentiation