The detailed in vitro and in vivo results have authenticated that the PCP-Mn-DTA@GOx@1-MT nanosystem not only strategically overcomes the biobarriers and improves the delivery efficiency via the weakly acidic tumor microenvironment-sensitive size/charge transition, but also effectively reinforces the immune response activation with reduced immune tolerance via the GOx-activated starvation/oxidation therapy and IDO-blockade immunotherapy. Here, IDO1 is linked to neoplasm.