Tumor Protection by IL-7 Secreting Whole Cell Vaccine is Merely Mediated by NK1.1-positive Cells
Tumor Protection by IL-7 Secreting Whole Cell Vaccine is Merely Mediated by NK1.1-positive Cells
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DOI：
10.1097/cji.0b013e318242514b
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发表时间：
2012-02-01
影响因子：
3.9
通讯作者：
Kraaij, Robert
中科院分区：
文献类型：
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作者：
Schroten, Caroline;Scheffer, Reinilde;Kraaij, Robert
由于前列腺上皮细胞组成性产生白细胞介素7（IL-7），也负责T细胞和NK细胞的发育和止血，因此重要的是要检查其预防前列腺癌的能力，以及其在未来前列腺癌疫苗策略中的可能作用。RM-9/mIL-7细胞用作分泌mIL-7的全细胞疫苗，以防止C57 bl/6小鼠中皮下RM-9攻击后的肿瘤生长。在C57 bl/6小鼠中通过CD 3（+）、CD 4（+）、CD 8（+）或NK1.1（+）耗竭实验研究RM-9/mIL-7疫苗接种效果。RM-9/mIL-7免疫小鼠的存活时间比未免疫小鼠长（P < 0.0001）。未接种小鼠的耗竭显示CD 3（+）、CD 4（+）、CD 8（+）和NK 1.1（+）细胞分别减少97%、56%、99%和88%。RM-9/mIL-7免疫小鼠，CD 3（+）、CD 4（+）、CD 8（+）或NK 1.1（+）耗竭，与非耗竭免疫小鼠组相比，均显示宿主存活时间缩短。此外，与未耗尽的RM-9/mIL-7疫苗接种组相比，更少的小鼠在肿瘤攻击中存活。观察到NK1.1（+）缺失小鼠的存活时间最短，与未接种疫苗小鼠的存活时间几乎相当。RM-9/mIL-7免疫小鼠在肿瘤攻击给药后的存活时间比未免疫小鼠的存活时间延长。在RM-9/mIL-7疫苗接种后，检测到的针对RM-9肿瘤攻击的免疫应答显示仅与NK1.1表达细胞相关。前列腺上皮细胞自身产生的IL-7和NK1.1表达细胞的作用可以为未来的免疫治疗模式提供新的潜力，以招募免疫细胞对抗前列腺癌及其转移。
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.