Tumor protection by IL-7 secreting whole cell vaccine is merely mediated by NK1.1-positive cells

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. Copyright

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