Orchestrating intratumoral DC-T cell immunity for enhanced tumor control via radiotherapy-activated TLR7/8 prodrugs in mice.

ABSTRACT: Optimizing intratumoral dendritic cell (DC)-T cell responses is pivotal for effective cancer immunotherapy. However, the mechanistic governing these dynamics within the tumor microenvironment (TME) remains unclear, and strategies to improve their therapeutic potential are underexplored. Here, we show that precise radiotherapy activates the pro-TLR7/8 agonist imidazoquinoline (IMDQ) locally in preclinical tumor models, stimulating DCs to elicit T cell immunity without the need for further recruitment or causing systemic toxicity. Mechanistically, this synergistic approach triggers type I interferon via STING and MyD88 signaling pathways, strengthening local immune responses. Importantly, we reveal that fractionated, low-dose radiotherapy can effectively optimize local DC-T cell dynamics to

SUBMITTER: Yin X 

PROVIDER: S-EPMC12216172 | biostudies-literature | 2025 Jul

REPOSITORIES: biostudies-literature