Experimental study of individualized cancer immunotherapy based on dendritic cells against gastric cancer / 中华外科杂志

ABSTRACT

<p><b>OBJECTIVE</b>To investigate the antitumor effects of cytotoxic T lymphocytes (CTLs) induced by autologous dendritic cells that were inspired by autologous tumor lysates (ATLs-mDCs).</p><p><b>METHODS</b>Primary gastric cancer cells prepared by short-term culture were used as targets. ATLs-mDCs were subjected to activate autologous T cells to generate CTLs. The immunological functions of DCs were evaluated by flow cytometry and by mixed leukocyte response (MLR) assay. The antitumor outcome of tumor antigen specific CTLs was tested by cytotoxicity assay. Concentrations of IL-12 in cultured DCs and INF-gamma in CTLs were measured by ELISA.</p><p><b>RESULTS</b>The expressions of MHC-II, CD80, CD83 and CD86 were significantly up-regulated in ATLs-mDCs, moreover, the ATLs-mDCs obtained the capability of stimulating the proliferation of autologous T cells with high efficiency. The secretion of IL-12 in ATLs-mDCs was significantly higher than that in pure mature DCs (t = 15.47, P < 0.01) and in immature DCs (t = 28.44, P < 0.01). The secretion of INF-gamma in CTLs activated by ATLs-mDCs was significantly higher than that in CTLs by pure mature DCs (t = 4.84, P < 0.05) and in CTLs by immature DCs (t = 13.74, P < 0. 01). The antigen specific cytotoxicity of CTLs induced by ATLs-mDCs was significantly higher against autologous tumor cells [(84 +/- 11)%] than that against two allogeneic tumor cell lines [(19 +/- 7)% and (19 +/- 11)%; t = 54.18 and 56.46, P < 0.01, respectively].</p><p><b>CONCLUSIONS</b>ATLs-mDCs might mediate the antigen specific CTLs against autologous gastric cancer cells ex vivo with high efficiency.</p>