Bimodal Imaging-Guided Temporal Optimization of Combined Chemotherapy and DC Vaccine Immunotherapy

Dendritic cell (DC) vaccines represent a clinically promising strategy for cancer treatment using a "prime-boost" approach. Achieving synergistic antitumor efficacy with chemotherapy requires precise temporal coordination, yet the timing of post-chemotherapy vaccination remains unstandardized, hindering its clinical translation. To address this, we designed a nanoprobe (Fe@O-DT(Cy7)) and applied bimodal imaging (FMI/MPI) to track DC vaccine migration and apoptosis after oxaliplatin treatment in a colorectal cancer model. We identified an optimal therapeutic window on day 7 post-chemotherapy, coinciding with peak immunogenic cell death (ICD). DC vaccination within this 7-d window ensured optimal lymph node homing, minimal apoptosis, and enhanced antitumor efficacy, characterized by immune cell infiltration and tertiary lymphoid structure (TLS) formation. Mechanistically, this window correlated with NF-κB pathway activation and CCL19/CCL21 upregulation. This study elucidates the role of the LTα1β2-LTβR axis in ICD-modulated DC vaccination and reveals the function of TLS in DC vaccine efficacy.