Dendritic cells as programmable platforms for cancer immunotherapy.

Dendritic cells (DCs) are professional orchestrators of the immune system, integrating environmental signals to initiate, modulate, and sustain antitumor immunity. Although their therapeutic potential extends beyond antigen delivery, most clinical strategies have used DCs primarily as cellular vaccines. Here, we propose that DCs should be viewed as programmable therapeutic cells whose functions can be rationally controlled, either in situ or ex vivo, through four variables: DC identity, antigenic input, anatomical site of action, and immune-instructive output. Together, these variables determine how DCs establish tissue-level immune circuits for tumor control. We further discuss how tumor-associated barriers determine DC programming requirements and how matching DC programs to these microenvironmental or systemic barriers may improve tumor control in patients with cancer.