In vitro study on anti-esophageal cancer immunity induced by antigen-sensitized and interleukin 27 gene-modified dendritic cells
10.3781/j.issn.1000-7431.2011.07.006
- Author:
Lei WANG
1
Author Information
1. Department of Thoracic Surgery
- Publication Type:Journal Article
- Keywords:
Antigen-sensitization;
Dendritic cells;
Esophageal neoplasms;
Immunotherapy;
Interleukin-27;
Transfection
- From:
Tumor
2011;31(7):601-607
- CountryChina
- Language:Chinese
-
Abstract:
Objective: To investigate the anti-esophageal cancer immunity induced by antigen-sensitized and interleukin 27 (IL -27) gene-modified dendritic cells (DCs). Methods: DCs isolated from the peripheral blood of patients with esophageal cancer were modified by recombinant retrovirus-mediated IL -27 gene, and then sensitized by the cleaved products from esophageal carcinoma Eca109 cells by using repeated freezing-thawing method. The secretion levels of IL-27, IL-12 and interferon-γ (IFN-γ) in culture supernatant of DCs and the level of IFN-γ in cytotoxic T lymphocytes (CTLs) were examined by ELISA method. The expression levels of CD1a, CD83, CD80 and CD86 molecules on DCs surface were measured by FCM. The proliferative activity of T lymphocytes and the killing efficacy of CTLs against Eca109 cells induced by DCs were evaluated by MTT method. Results: After being modified by IL -27 gene and sensitized by tumor antigen, the secretion levels of IL-12[(107.85±7.20) ng/L], IL-27[(430.39±10.12) ng/L] and IFN-γ[(411.97±17.80) ng/L] of DCs were increased, and the expressions of CD83[(82.67±7.92)%], CD80[(78.33±7.31)%] and CD86[(85.33±4.32)%] molecules were also elevated. Meanwhile, the proliferation capacity of autologous T lymphocytes was enhanced after stimulation by DCs, and the secretion level of IFN-γ[(751.50±31.30) ng/L] in the culture supernatant of DCs was increased. The DCs modified by IL -27 gene and sensitized by tumor antigen could significantly induce the strongest cytotoxicity of antigen-specific CTLs against Eca109 cells (P<0.01). Conclusion: IL -27 gene modification enhances the capacity of DCs in inducing autologous T lymphocytes to generate specific antitumor immunity against esophageal carcinoma. The mechanism of this immune response may be closely relevant to the activation of the second signal for presenting antigen cells such as DCs, the promoted capacity of DCs secreting IL-27 and IL-12, and the activation of T cells resulting in the enhanced capacity of CTLs excreting IFN-γ. Copyright© 2011 by TUMOR.