Supplemental Figures 1 - 7 PDF 2666K, Supplemental Figure 1. Priming with DC-Tag induces a long-lasting antigenspecific immune response. Supplemental Figure 2. Boosting increases the absolute number of rapidly responding Ag-specific CD8+ splenocytes. Supplemental Figure 3. Boosting does not increase the cytolytic activity of Tagspecific CD8+ T cells. Supplemental Figure 4. Repeated DC-Tag boosting helps maintaining the pool of Ag-specific CD8+ TCM cells. Supplemental Figure 5. Different vaccination schedules do not impact on the pool of Ag-specific CD8+ TCM cells.Supplemental Figure 6. A larger pool of Ag-specific CD8+ TCM cells ensures better protection against tumor challenge. Supplemental Figure 7. Donor-derived CD8+ T cells lead the Tag specific immune response in transplanted TRAMP mice
ARTICLE ABSTRACTAlthough cancer vaccines are in the clinic, several issues remain to be addressed to increase vaccine efficacy. In particular, whether how and how frequently a patient should be boosted remains to be defined. Here, we have assessed the ability of dendritic cell (DC)-based vaccines to induce a long-lasting tumor-specific CTL response in either prophylactic or therapeutic settings by taking advantage of transplantable and spontaneous mouse tumor models. Implementing a 24-hour ex vivo intracellular cytokine production assay, we have found that priming with a DC-based vaccine induced a long-lasting CTL response in wild-type mice, and homologous boosting better sustained the pool of central memory T cells, which associated with potent protection against B16F1 melanoma challenge. Appropriate timing of booster vaccination was also critical, as a tight boosting schedule hindered persistence of IFN-γ–competent memory CD8+ T cells and mice survival in prophylactic settings. Conversely, prime/boost vaccination proved to be of no advantage or even detrimental in therapeutic settings in B16F1 and transgenic adenocarcinoma of the mouse prostate (TRAMP) models, respectively. Although DC priming was indeed needed for tumor shrinkage, restoration of immune competence, and prolonged survival of TRAMP mice, repeated boosting did not sustain the pool of central memory CTLs and was detrimental for mice overall survival. Thus, our results indicate that booster vaccinations impact antitumor immunity to different extents, depending on their prophylactic or therapeutic administration, and suggest evaluating the need for boosting in any given patient with cancer depending on the state of the disease. Cancer Res; 73(12); 3545–54. ©2013 AACR.