Department of Hematology, Second Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, 710004 Shaanxi Province, China.
Med Oncol. 2012 Sep;29(3):2261-9. doi: 10.1007/s12032-011-0024-8. Epub 2011 Jul 15.
Homeostasis-driven proliferation of T cells is an important means of reconstituting T-cell-dependent immunity after lymphodepletion regimens, such as chemotherapy or radiotherapy. Immune-reconstituted mice that receive a tumor vaccine mount more efficient anti-tumor immune responses compared with control mice. In the present study, we evaluated the anti-tumor immune responses in immune-reconstituted mice vaccinated with inactivated leukemia cells and explored the mechanisms underlying these immune responses. Test C57BL/6 mice were lymphodepleted by irradiation and immune-reconstituted with naïve mouse spleen lymphocytes. Mice were then injected with an inactivated FBL-3 tumor cell vaccine and challenged with FBL-3 tumor cells. Anti-tumor responses were evaluated by determining the rate of tumor formation, latency, tumor size, interferon gamma levels, and macrophage and CTL cytotoxicities. When challenged with tumor cells, immune-reconstituted, vaccinated mice exhibited a significantly lower mortality, smaller average tumor volume, and a significantly longer mean survival time. They had more robust cellular immunity, reflected by higher levels of INF-γ production and higher macrophage- and CTL-mediated cytotoxicities. Our results suggest that immune reconstitution enhanced the anti-tumor immune responses in mice injected with a tumor vaccine via generation of CTLs. These results have important implications for immunotherapy used for leukemia.
在化疗或放疗等淋巴耗竭方案后，通过细胞的稳态增殖来重建 T 细胞依赖的免疫是一种重要的手段。与对照组小鼠相比，接受肿瘤疫苗免疫重建的小鼠会产生更有效的抗肿瘤免疫反应。在本研究中，我们评估了用灭活白血病细胞免疫重建的小鼠的抗肿瘤免疫反应，并探索了这些免疫反应的机制。实验选用 C57BL/6 小鼠，通过照射进行淋巴耗竭，并用幼稚的小鼠脾淋巴细胞进行免疫重建。然后，将小鼠用灭活的 FBL-3 肿瘤细胞疫苗进行免疫接种，并接受 FBL-3 肿瘤细胞的攻击。通过测定肿瘤形成率、潜伏期、肿瘤大小、干扰素 γ 水平以及巨噬细胞和 CTL 细胞毒性来评估抗肿瘤反应。当受到肿瘤细胞攻击时，接受疫苗免疫重建的小鼠的死亡率显著降低，平均肿瘤体积更小，平均存活时间显著延长。它们具有更强的细胞免疫，表现为更高水平的 INF-γ 产生和更高的巨噬细胞和 CTL 介导的细胞毒性。我们的结果表明，通过生成 CTL，免疫重建增强了接受肿瘤疫苗注射的小鼠的抗肿瘤免疫反应。这些结果对于白血病的免疫治疗具有重要意义。
