Accelerating Tumor Immunotherapy Through a Synergistic Strategy of Increasing Throttle and Relaxing Brake

Abstract Tumor immunotherapy has been widely used clinically, but it is still hindered by weak antitumor immunity and immunosuppressive tumor microenvironment (TME). Here, a kind of simple disodium hydrogen phosphate nanoparticle (Na 2 HPO 4 NP) is prepared to “accelerate” tumor immunotherapy by “increasing throttle” and “relaxing brake” simultaneously. The obtained Na 2 HPO 4 NPs release a large amount of Na + and HPO 4 2− ions within tumor cells, thereby activating the caspase 1/GSDMD‐mediated pyroptosis pathway to achieve immune activation. Meanwhile, alkalescent Na 2 HPO 4 NPs can further consume lactic acid through acid‐base neutralization, and regulate adenosine (Ado) metabolism via nanomaterial‐induced biocatalytic process to relieve two‐tier immunosuppression. Collectively, Na 2 HPO 4 NPs effectively activate the antitumor immune process in vivo, and dramatically inhibit primary and distal tumor growth. This work will provide unique inspiration and strategy for the regulation of both positive and negative directions in immunotherapy.