Interleukin-18 enhances specific antitumor activity of CTL induced by tumor antigen plused dendritic cells
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Abstract:
Objective: To study whether interleukin(IL)18 can promote tumor antigenpulsed dendritic cells (DCs) to induce specific CTL against hepatocellular carcinoma(HCC) in vitro. Methods: The recombinant adenovirus expression plasmid AdIL18 was transfected into DCs pulsed by HepG2 lysates (AdIL18HepG2/DC). The surface molecules of AdIL18HepG2/DCs were analyzed by flow cytometry. IL18 levels in culture supernatant of AdIL18HepG2/DCs were measured by ELISA. The ability of AdIL18HepG2/DC to induce proliferation of autologous T lymphocytes was evaluated by 3HTdR assay. The in vitro CTL antitumor activity induced by AdIL18HepG2/DC on HepG2 cell was detected by MTT. Results: IL18 promoted expression of CD1a, CD11c, CD80, CD86 and HLADR on HepG2/DCs compared with untransfected DCs. AdIL18HepG2/DCs secreted more IL18 in vitro compared with untransfected DCs. AdIL18HepG2/DC effectively stimulated proliferation of autologous T cells ( CPM being 228 018 ±1 079); the stimulating effect was significantly higher than those of AdIL18DC, HepG2/DC, AdlzcZ/DC, and DC(all P<0.05). CTL induced by TAA pulsed/IL18 modified DC had significantly higher cytotoxicity against HepG2 cells compared with that induced by other DCs. Conclusion: AdIL18HepG2/DCs have enhanced ability to induce specific CTL in killing hepatocellular carcinoma HepG2 cell line.
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Surpported by the National Natural Science Foundation of China (No.30672391); the Medical and Health Foundation of the PLA(No.06MA205); the Natural Science Foundation of the Shaanxi Province (No.2004C222)