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.