关键词：免疫疗法;前列腺癌;T淋巴细胞;细胞(生物学);细胞因子
摘 要：Adoptive cell therapy (ACT) of cancer with ex vivo activated/expanded T-cells is one of the promising treatments currently being tested in patients. One challenge of the approach is that the transferred T cells become functionally anergic in the tumor environment, limiting their anti- tumor effect. We have investigated whether tumor-mediated immune suppression can be overcome by arming tumor-specific T cells with cytokine/immunostimulator- loaded nanoparticles carried by each cell. Specially, we have defined the role of CD70 and CD80/CD86 in dendritic cell-mediated activation of tumor tolerized CD8 T cells, discovered the effect of CD8 T cell responses in selecting for antigen-negative tumor cells, and develop a better prostate model for monitoring T cell responses to prostate cancer in mice. Findings from our studies identify molecular interactions that are important for maintaining T cell function in the tumor environment, suggesting possible interventions to enhance T cell functionality during ACT. Our results 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 provide insights into the requirements for an effective cancer immunotherapy: not only inducing potent immune responses but also avoiding selection and outgrowth of antigen- negative tumor cells.