Mechanism of antitumor effects of Hepa1ª²6 cells fused with geneª²modified dendritic cells

    SONG Wenª²Gang, QU Xun, CHEN Xianª²Rui, LI Yaª²Lin, LI Song, WU Cong

    1Department of Immunology, School of Basic Medicine, Taishan Medical College, Tai¡¯an 271000, China, 2Institute of Basic Medicine, Qilu Hospital, Shandong University, Jinan 250012, China

    ¡¾Abstract¡¿ AIM: To investigate the mechanism of antitumor effects of tumor fusion vaccines of adenovirusª²mediated ILª²18 geneª²modified dendritic cells (DC) with hepalª²6 cells (ILª²18ª²DCª²Hepa fusion vaccines). METHODS: NK cell activity was detected by 4 h 51Cr releasing assay and the antitumor immune response of immunocytes subsets and immune molecules induced by ILª²18ª²DCª²Hepa fusion vaccines was detected by in vivo depletion assay. Geneª²deficient tumorª²bearing mice models were established and the immunotherapy effects of the ILª²18ª²DCª²Hepa fusion vaccines were detected. RESULTS: Immunization with ILª²18ª²DCª²Hepa fusion vaccines effectively induced more potent NK cell activity compared with DCª²Hepa fusion vaccines [(42.5¡À4.7)% vs (13.5¡À2.2)%, q=20.8, P<0.01]. Protective immunity induced by ILª²18ª²DCª²Hepa fusion vaccines was dependent on CD4+ T cells [(67.8¡À6.1) mm2, q=28.3, P<0.01], CD8+ T cells [(58.9¡À6.2) mm2, q=24.4, P<0.01], NK cells [(30.6¡À4.5) mm2, q=12.0, P<0.01], B7/CD28 pathway of T cell costimulation [(75.4¡À6.5) mm2, q=31.6, P<0.01] and IFNª²¦Ã [(62.3¡À6.8) mm2, q=25.9, P<0.01] in the induction phase while in the effective phase, it was on CD8+ T cells [(68.9¡À4.5) mm2, q=42.3, P<0.01], NK cells [(38.6¡À3.3) mm2, q=22.7, P<0.01], IFNª²¦Ã [(74.4¡À5.8) mm2, q=45.8, P<0.01] rather than CD4+ T cells [(4.2¡À1.9) mm2, q=0.4, P>0.05]. Compared with C57BL/6 tumorª²bearing mice, the therapeutic effects of ILª²18ª²DCª²Hepa fusion vaccines on IFNª²¦ÃR geneª²deficient tumorª²bearing mice were obviously decreased [(60.1¡À6.7) mm2 vs (4.1¡À1.8) mm2, t¡ä=19.77, P<0.01]. CONCLUSION: The antitumor responses of ILª²18ª²DCª²Hepa fusion vaccines may be closely associated with CD4+ T cells, CD8+ T cells, NK cells, CD28/B7 pathway of T cell costimulation and IFNª²¦Ã. ......