Li Qi-ling, Gao Shang-feng, Wang Yun-ping, Ma Jun, Feng Cai-xia, Wang Ying, Wang Yue-ling
Department of Gynecology and Obstetrics, the First Affiliated Hospital of Xi'an Jiaotong University, Shan Xi, China.
Ann Saudi Med. 2012 Mar-Apr;32(2):162-8. doi: 10.5144/0256-4947.2012.162.
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 naïve 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-γ 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.
淋巴细胞减少期间接种疫苗可能促进对弱自身抗原的免疫反应并增强抗肿瘤免疫力。本研究的目的是确定肿瘤疫苗免疫疗法联合使用荷瘤宿主免疫细胞进行免疫重建在淋巴细胞减少中的有效性，并研究免疫疗法期间体外激活的荷瘤宿主T细胞的作用。
2009年1月至2010年1月在西安交通大学第一附属医院进行的动物研究。
用环磷酰胺诱导淋巴细胞减少。采用不同同基因淋巴细胞重建免疫系统，包括来自未致敏大鼠的淋巴细胞（未致敏组）、荷瘤大鼠的淋巴细胞（荷瘤组）和体外激活的荷瘤大鼠的淋巴细胞（激活组）。所有大鼠均用粒细胞-巨噬细胞集落刺激因子（GM-CSF）修饰的NuTu-19卵巢癌细胞（GM-CSF/NuTu-19）进行免疫接种。收集肿瘤疫苗引流淋巴结（TVDLN），然后刺激诱导效应T细胞（T(E)）。然后将T(E)过继转移至预先建立腹部肿瘤3天的大鼠（NuTu-19），并计算存活率。
与未致敏组相比，荷瘤组白细胞介素-2（IL-2）水平显著降低，而IL-4水平显著升高（P<0.05）。分泌干扰素-γ的CD4+T细胞数量和CD8+细胞毒性T淋巴细胞的特异性细胞毒性显著降低（P<0.05）。与其他组相比，激活组的存活率显著更高。
体外激活的荷瘤大鼠淋巴细胞可有效逆转荷瘤宿主的免疫抑制作用。
