In vitro-activated tumor-bearing host T cells and the effectiveness of tumor vaccine immunotherapy

ABSTRACT

Vaccination during periods of lymphopenia may facilitate immune responses to weak self-antigens and enhance antitumor immunity. The objective of this study was to determine the effectiveness of tumor vaccine immunotherapy combined with immune reconstruction using tumor-bearing host immune cells in lymphopenia, and to investigate the role of tumor-bearing host T cells activated in vitro during immunotherapy. Animal study conducted in the First Affiliated Hospital of Xi'an Jiaotong University from January 2009 to January 2010. Lymphopenia was induced by cyclophosphamide. A reconstituted immune system with different syngeneic lymphocytes was employed, including lymphocytes from naive rats [unsensitized group], tumor-bearing rats [tumor-bearing group], and tumor-bearing rats activated in vitro [activated group]. All rats were immunized with granulocyte-macrophage colony-stimulating factor [GM-CSF]-modified NuTu-19 ovarian cancer [GM-CSF/NuTu-19] cells. Tumor vaccine-draining lymph nodes [TVDLNs] were harvested, and then stimulated to induce effector T cells [T[E]]. T[E] were then adoptively transferred to rats bearing a 3-day pre-established abdominal tumor [NuTu-19], and the survival rate was calculated. Compared with the unsensitized group, the levels of interleukin-2 [IL-2] were significantly lower in the tumor-bearing group, whereas that of IL-4 were significantly higher [P<.05]. The number of CD4+T cells secreting interferon-gamma and the specific cytotoxicity of CD8+ cytotoxic T lymphocytes were significantly lower [P<.05]. The survival was significantly higher in the activated group compared with the other groups. Lymphocytes from tumor-bearing rats activated in vitro can effectively reverse the immunosuppressive effects of tumor-bearing hosts