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目的利用淋巴细胞减少期T细胞发生增殖活化的原理,以全身照射或环磷酰胺引起淋巴细胞减少,联合免疫重建及肿瘤疫苗免疫,以增强机体的肿瘤特异性免疫反应。方法分别以放疗或化疗(环磷酰胺)引起小鼠淋巴细胞减少,然后输入同系小鼠的未致敏脾细胞,建立免疫重建的淋巴细胞减少小鼠模型(RLM)。用黑色素瘤细胞F10对前者行免疫肿瘤攻击实验,并行T细胞亚群清除试验。而化疗RLM免疫模型的抗肿瘤免疫反应效果通过过继免疫治疗检测。免疫用瘤苗为GMCSF修饰的黑色素瘤细胞D6G6。免疫后9～10d,采集肿瘤疫苗接种部位的引流淋巴结,制备效应T细胞,然后过继回输给荷瘤3d(D5)的小鼠。2周后处死小鼠,计数肺转移灶数目。结果63.2%的放疗RLM免疫组小鼠可对肿瘤攻击产生抵抗,显著高于正常免疫组(16.7%,P<0.0001)。CD8+T细胞是介导抗肿瘤保护性免疫的主要效应细胞。延长免疫重建和瘤苗接种之间的间隔可削弱保护性抗肿瘤免疫。化疗RLM免疫组效应T细胞的在体抗肿瘤活性显著强于正常免疫组。结论在放、化疗引起的淋巴细胞减少期进行瘤苗免疫,有助于打破机体对肿瘤的免疫耐受,增强抗肿瘤免疫反应。
Objective To utilize the principle of proliferation and activation of T lymphocytes in lymphopenia, and to induce systemic lymphocytes or cyclophosphamide-induced lymphocytopenia, combined with immune reconstitution and tumor vaccine to enhance the tumor-specific immune response. Methods Lymphopenia was induced in mice by radiotherapy or chemotherapy (cyclophosphamide), respectively, and then splenocytes were injected into non-sensitized splenocytes of homologous mice to establish an immunosuppressed lymphopenic mouse model (RLM). Immuno-tumor challenge experiments were performed on the former with melanoma F10 cells and parallel T cell subpopulation clearance tests were performed. The anti-tumor immune response to chemotherapeutic RLM immunosuppression was tested by adoptive immunotherapy. The vaccine for immunization was GMCSF-modified melanoma cell D6G6. Nine to ten days after immunization, draining lymph nodes at the site of tumor vaccination were collected to prepare effector T cells, which were then adoptively transfused into the tumor-bearing mice (D5). Mice were sacrificed after 2 weeks and the number of lung metastases was counted. Results 63.2% of the mice in the RLM-treated group were more resistant to tumor challenge than those in the normal group (16.7%, P <0.0001). CD8 + T cells are the main effector cells that mediate anti-tumor protective immunity. Prolonging the interval between immune reconstitution and tumor vaccination weakens protective anti-tumor immunity. The antitumor activity in vivo of RLM immunized group was significantly higher than that of normal immunized group. Conclusions The immunization of tumor vaccine in radiotherapy and chemotherapy-induced lymphopenia can help to break the body’s immune tolerance to tumor and enhance the anti-tumor immune response.