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Therefore, a two\u2010pronged approach, encompassing the activation of immunogenic cell death (ICD) and blocking the indoleamine 2,3\u2010dioxygenase (IDO)\u2010mediated pathway, is devised to elicit systemic anti\u2010tumor immunity and alleviate immunosuppression. Herein, a tumor microenvironment (TME)\u2010specific driven nanoagent is composed\u00a0of a tetrasulfide bond\u2010bridged mesoporous silica layer (MON) coated up\u2010conversion nanoparticles as a nano\u2010carrier, combines Fe<jats:sup>2+<\/jats:sup>, curcumin, and indoximod for operating chemodynamic therapy\/chemotherapy\/immunotherapy. The consumption of glutathione (GSH) caused by MON degradation, the Fenton reaction of Fe<jats:sup>2+<\/jats:sup>, and curcumin triggering mitochondrial damage collectively exacerbate the oxidative stress, leading to a violent immunoreaction and reversal of the immunosuppressive TME through a combination of IDO\u2010inhibitors. 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