Study of Immune Responses after Multiple Autologous Whole Cervical Tumor Cell Vaccination in TC-1 Mouse Model

• Main Authors: Yu Sing Chen, 陳郁欣
• Other Authors: J. T. Qiu
• Format: Others
• Published: 2015
• Online Access: http://ndltd.ncl.edu.tw/handle/24491702966089944693

碩士 === 長庚大學 === 生物醫學研究所 === 103 === The antigens of tumor cells are highly similar to those in the normal host cells, suggesting that they are not easily recognized by the host immune system. Early research found that immunization with tumor cell based vaccines may effectively induce tumor antigen-specific T cell activation and proliferation. Granulocyte-macrophage colony-stimulating factor (GM-CSF) has been broadly used as adjuvant with DNA vaccines and tumor vaccines. Immunizations with codon-optimized GM-CSF plasmid DNA-vaccine result in an effective cytotoxic T lymphocyte response. Previous studies have shown that a highly-productive GM-CSF -based tumor cell vaccine may induce immune-suppressive effects that are dependent on the number of immunization. However, in this study, we found that different numbers of vaccinations resulted in different tumor rejection effects. Thus, we hypothesized that the GM-CSF-secreting tumor cell vaccine induces tumor rejection and improves prognosis after tumor cell challenge, which may be associated with interferon-producing killer dendritic cell (IKDC) activation. In this study, we used the high GM-CSF-producing TC-1 cells as a tumor cell vaccine that, simultaneously expresses the HPV E6 and E7 oncoproteins. The mice were subcutaneously injected either one, three or five times. The mice were then sacrificed, and the frequencies of Treg cell and IKDC in splenocytes were analyzed via flow cytometry. We found that the percentage of Treg cells in splenocytes is associated with the number of immunizations; however, this association was not only due to tumor rejection and survival. The IKDC percentage in the splenocytes from the group of 3 times vaccinations was significantly higher than the other groups, which showed a similar trend with survival rate. These data suggest that the efficacy of tumor rejection was not only associated with Treg cell effects but also the activation of IKDC proliferation.