Stimulation of patients' immune systems for the treatment of solid tumors is an emerging therapeutic paradigm. The use of enriched autologous T cells for adoptive cell therapy (ACT) or vaccination with antigen-loaded dendritic cells have shown clinical efficacy in melanoma and prostate cancer, respectively. However, the long-term effects of immune responses on selection and outgrowth of antigen-negative tumor cells in specific tumor types must be determined in order to understand and achieve long term therapeutic effects. In this study, we have investigated the expression of a tumor specific antigen in situ after treatment with tumor specific CD8+ T cells in an autochthonous mouse model of prostate cancer. After T cell treatment, aggregates of dead antigen-positive tumor cells were concentrated in the lumen of prostate gland and were eventually eliminated from the prostate tissue. Despite the elimination of antigen-positive tumor cells, prostate tumor continues to grow in T cell treated mice. Interestingly, remaining tumor cells were antigen-negative and downregulated MHC class I expression. These results show that CD8+ T cells are effective in eliminating antigen-bearing prostate tumor cells but they also can select for the outgrowth of antigen-negative tumor cells. These findings provide insights into the requirements for an effective cancer immunotherapy within the prostate: not only inducing potent immune responses but also avoiding selection and outgrowth of antigen-negative tumor cells.
- Received July 31, 2013.
- Revision received September 16, 2013.
- Accepted September 17, 2013.
- Copyright © 2013, American Association for Cancer Research.