Dendritic cells (DCs) are key antigen-presenting cells that initiate anti-tumor immunity, with cDC1s playing a critical role in cross-presentation and CD8⁺ T cell activation. However, within the immunosuppressive tumor microenvironment (TME), DC infiltration and maturation are often impaired, limiting effective immune responses. 

Calcium ion (Ca²⁺) is an essential second messenger, regulating DC activation, antigen presentation, and migration. Here, we report calcium carbonate nanoparticles (αCaNPs) that elevate intracellular Ca²⁺ levels upon uptake by DCs. This promotes cDC1 tumor infiltration via upregulation of chemokine receptors, enhances DC maturation and antigen processing, and induces CCR7 expression to facilitate migration to draining lymph nodes. These effects collectively amplify T cell-mediated anti-tumor immunity. 

In vivo, αCaNPs demonstrate significant anti-tumor efficacy, particularly in combination with radiotherapy or immunotherapy. This work highlights a calcium-modulating nanoplatform to restore DC function and improve cancer immunotherapy.