Dendritic cell-derived exosomes from PDT-treated glioma cells enhance antitumor immunity as a subcellular vaccine

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BACKGROUND: Glioma is a highly aggressive brain tumor with a poor prognosis. Photodynamic therapy (PDT) induces antitumor immunity, a key mechanism of its efficacy. Dendritic cell-derived exosomes (Dexs) are crucial for tumor antigen presentation and T-cell activation. Dexs represent a promising cell-free strategy for cancer immunotherapy. Understanding the role of Dexs in PDT-induced immunity may enhance PDT efficacy. METHODS: GL261 glioma cells were subjected to PDT, followed by co-culture with dendritic cells (DC) to obtain PDT-Dexs. Flow cytometry and ELISA were used to assess the effects of PDT-Dexs on DC maturation and T-cell activation. MicroRNA sequencing was performed on PDT-Dexs. The effect of PDT-Dexs on tumor growth and survival was evaluated in immune-competent and immune-deficient glioma model mice. RESULTS: Co-incubation with PDT-Dexs significantly increased DC maturation and T-cell activation. Sequencing revealed 156 up-regulated microRNAs, miR-152-3p was validated as a key functional miRNA that promotes DC maturation by targeting DNMT1 to upregulate MyD88 expression. PDT-Dexs entered the systemic circulation, increasing the serum IL-2, IFN-γ, and TNF-α levels. In immunocompetent mice, PDT-Dexs increased CD3 + CD4+ and CD3 + CD8+ T-cell percentages, slowed tumor growth, prolonged survival, and were associated with enhanced CD8 + T-cell infiltration and tumor cell apoptosis. Crucially, PDT-Dexs failed to inhibit tumor growth or improve survival in immunodeficient nude mice. CONCLUSIONS: PDT-Dexs promote DC maturation and T-cell activation, improving antitumor immunity and PDT efficacy. Combining of PDT with PDT-Dexs further improves antitumor immunity and PDT efficacy. PDT-Dexs warrants further investigation as a potential strategy for enhancing antitumor immunity in glioma.

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