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

ABSTRACT: 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.

ORGANISM(S): Mus musculus

PROVIDER: GSE325822 | GEO | 2026/04/02

REPOSITORIES: GEO

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			Action	DRS
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	GSE325822_all_compare_LN.txt.gz	Txt
	GSE325822_all_compare_TUMOR.txt.gz	Txt

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Project description:Gliomas are the most frequent type of primary tumor of the central nervous system in adults with significant morbidity and mortality. Despite the development of novel, complex, multidisciplinary, and targeted therapies, glioma therapy has not progressed much over the last decades. Therefore, there is an urgent need to develop novel patient-adjusted immunotherapies that actively stimulate antitumor T cells generating long-term memory and thus resulting in significant clinical benefits. This work aimed to investigate the efficacy and molecular mechanism of dendritic cell (DC) vaccines loaded with glioma cells undergoing immunogenic cell death (ICD) induced by photosens based photodynamic therapy (PS-PDT) and to identify reliable prognostic genes’ signatures for predicting patients’ overall survival (OS). The analysis of the transcriptional program of the ICD-based DC vaccine led to the identification of robust induction of Th17 signature when used as a vaccine, these DCs demonstrate retinoic acid receptor-related orphan receptor-γt dependent efficacy in orthotopic mouse model. Moreover, by comparative analysis of transcriptome program of the ICD-based DC vaccine with transcriptome data from the TCGA-low grade glioma (LGG) dataset the four-gene signature (CFH, GALNT3, SMC4, VAV3) associated with OS of glioma patients have been identified. This model has been validated on OS of CGGA-LGG, TCGA-glioblastoma multiforme (GBM) and CGGA-GBM datasets to determine whether it has a similar prognostic value. For this the sensitivity and specificity of the prognostic model for predicting the OS were evaluated by calculating the area under curve (AUC) of the time-dependent receiver operating characteristic (ROC) curve. The values of AUC for TCGA-LGG, CGGA-LGG, TCGA-GBM and CGGA-GBM were, respectively, 0.75, 0.73, 0.9 and 0.69 for predicting 5-year survival rates. These data open attractive prospects for improving glioma therapy by employing ICD and PS-PDT-based DC vaccines to induce Th17 immunity and to use this prognostic model to predict the OS of glioma patients.

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

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