Reductive stress in cancer immunology and targeted therapy

• Reductive stress, characterized by excessive accumulation of reducing equivalents, disrupts redox homeostasis and can both inhibit tumor proliferation and impair immune cell function, acting as a context-dependent modulator in cancer-immune dynamics. • Unlike oxidative stress, reductive stress is not merely the inverse but involves distinct regulatory mechanisms and manifests as aberrant signaling, protein misfolding, mitochondrial dysfunction, and metabolic dysregulation. • Tumor cells and immune cells undergo metabolic reprogramming that can shift intracellular redox balance, influencing the tumor microenvironment and immune surveillance. • Targeting reductive stress represents a promising avenue for enhancing cancer immunotherapy efficacy, though research is still in its infancy.