Infiltration of tumor-reactive transforming growth factor-beta insensitive CD8+ T cells into the tumor parenchyma is associated with apoptosis and rejection of tumor cells

BACKGROUND. TGF-beta is a potent immunosuppressant. High levels of TGF-beta produced by cancer cells have a negative inhibition effect on surrounding host immune cells and leads to evasion of the host immune surveillance and tumor progression. In the present study, we report a distinct ability of tumor reactive, TGF-beta-insensitive CD8(+) T cells to infiltrate into established tumors, secrete relevant cytokiries, and induce apoptosis of tumor cells. METHODS. CD8(+) T cells were isolated from the spleens of C57BL/6 mice, which were primed with irradiated mouse Prostate cancer cells, the TRAMP-C2 cells. After ex vivo expansion, these tumor reactive CD8(+) cells were rendered TGF-beta-insensitive by infection with a retroviral (MSCV)-mediated dominant negative TGF-beta type II receptor (T beta RIIDN). Control CD8(+) cells consist of those transfected with the GFP-only empty vector and naive CD8(+) T cells. Recipient mice were challenged witha single injection of TRAMP-C2 cells 21 days before adoptive transfer of CD8(+) T cells was performed. Forty days after the adoptive transfer, all animals were sacrificed. The presence of pulmonary metastases was evaluated pathologically. Serial slides of malignant tissues were used for immunofluorescent staining for different kinds of immune cell infiltration, cytokines, and apoptosis analysis.