ErasmusMC, Department of Urology, Josephine Nefkens Institute, Rotterdam, The Netherlands.
J Immunother. 2012 Feb-Mar;35(2):125-30. doi: 10.1097/CJI.0b013e318242514b.
As prostatic epithelia constitutively produce interleukin 7 (IL-7), also responsible for the development and hemostasis of T cells and NK cells, it is important to examine its ability to protect against prostate cancer, and its possible role in future vaccine strategies against prostate cancer. RM-9/mIL-7 cells were used as mIL-7 secreting whole cell vaccine to prevent tumor growth upon a subcutaneous RM-9 challenge in C57bl/6 mice. The RM-9/mIL-7 vaccination effect was studied by CD3, CD4, CD8, or NK1.1 depletion experiments in C57bl/6 mice. RM-9/mIL-7-vaccinated animals showed longer survival times (P<0.0001) than nonvaccinated mice. Depletion of nonvaccinated mice showed a reduction of CD3, CD4, CD8, and NK1.1 cells with 97%, 56%, 99%, and 88%, respectively. RM-9/mIL-7-vaccinated mice, depleted for CD3, CD4, CD8, or NK1.1, all showed shortened host survival times with regard to the nondepleted vaccinated mice group. Moreover, fewer mice survived the tumor challenge compared with the nondepleted RM-9/mIL-7 vaccination group. The shortest survival was observed for NK1.1-depleted mice, which was nearly comparable with survival times of nonvaccinated mice. RM-9/mIL-7-vaccinated mice demonstrated prolonged survival times compared with the survival times of nonvaccinated mice, after tumor challenge administration. The detected immune response against the RM-9 tumor challenge showed to be merely related to the NK1.1-expressing cells, after RM-9/mIL-7 vaccination. IL-7 produced by the prostatic epithelia itself and the role of NK1.1-expressing cells could provide new potential for future immunotherapeutic modalities to recruit immunologic cells against prostate cancer, and its metastases.
由于前列腺上皮细胞持续产生白细胞介素 7(IL-7),该物质还负责 T 细胞和 NK 细胞的发育和止血,因此检查其预防前列腺癌的能力以及在未来针对前列腺癌的疫苗策略中的可能作用非常重要。RM-9/mIL-7 细胞被用作 mIL-7 分泌的全细胞疫苗,以防止 C57bl/6 小鼠皮下 RM-9 挑战后的肿瘤生长。通过在 C57bl/6 小鼠中进行 CD3、CD4、CD8 或 NK1.1 耗竭实验来研究 RM-9/mIL-7 疫苗的效果。RM-9/mIL-7 疫苗接种的动物的存活时间(P<0.0001)比未接种疫苗的动物长。非接种疫苗的耗竭小鼠显示 CD3、CD4、CD8 和 NK1.1 细胞分别减少 97%、56%、99%和 88%。CD3、CD4、CD8 或 NK1.1 耗竭的 RM-9/mIL-7 疫苗接种的小鼠,与未耗竭的疫苗接种小鼠组相比,均显示出宿主存活时间缩短。此外,与未耗竭的 RM-9/mIL-7 疫苗接种组相比,存活的小鼠更少。NK1.1 耗竭的小鼠观察到的存活时间最短,几乎与未接种疫苗的小鼠的存活时间相当。与非接种疫苗的小鼠相比,在肿瘤挑战后,RM-9/mIL-7 疫苗接种的小鼠显示出延长的存活时间。在 RM-9/mIL-7 疫苗接种后,针对 RM-9 肿瘤挑战的检测到的免疫反应仅与表达 NK1.1 的细胞有关。前列腺上皮细胞自身产生的 IL-7 和表达 NK1.1 的细胞的作用为针对前列腺癌及其转移的免疫治疗模式提供了新的潜力。