Implications of aging and self-tolerance on the generation of immune and antitumor immune responses.

摘要: Cancer statistics show a disproportionately higher burden of tumors in the old. Most studies evaluating vaccination strategies have not taken into consideration effect that aging has on immune system. For first time, we describe an animal tumor model which self-tolerance and are present at same time. FVB-Her-2/neu mice tolerant to neu antigens crossed with HLA-A2/Kb (A2xneu) develop spontaneous when they more than 22 months Analysis CD8(+) T-cell-specific responses A2xneu indicated priming activity old induce response was diminished compared young animals. Following intratumoral injections CpG-ODN, approximately 30% rejected tumor; however, no antitumor observed mice. T regulatory cells (Treg) there significantly Tregs After CpG-ODN plus Treg depletion, 70% tumor. The treatment prolonged survival mice, but none animals Even though depletion could rescue against self-tumor therapy is as effective hosts. Relevant models such time critical allow optimization effectively stimulate