Talk title Immunological Targeting of Cancer Stem Cells
SpeakerProf. Qiao LI
Research Associate Professor
Date & Time27 March 2019 (Wed)
VenueRoom G004, E12 Building (University of Macau)
AbstractThe existence of micro-metastasis at the time of tumor resection represents a significant therapeutic challenge, since 90% of tumor deaths are due to tumor metastasis.  Effective prevention of local and distant tumor recurrence remains to be developed.  There is increasing evidence that many cancers are driven and maintained by cancer stem cells (CSCs) which contribute to tumor recurrence and metastasis. Targeting CSCs may thus increase the therapeutic efficacy of current cancer treatment. We described a strategy to target CSCs using CSC-dendritic cell (DC) vaccination. However, the efficacy of CSC targeted therapeutics may be greatest when they are deployed in the adjuvant setting. In this study, two mouse models were utilized:   established such SCC7 tumors were surgically removed from mice followed by treatment using ALDHhigh SCC7 CSC-DC vaccine, which significantly reduced local tumor relapse and prolonged animal survival. This effect was significantly augmented by simultaneous administration of anti-PD-L1 mAb. In the minimal disease setting of D5 melanoma, ALDHhigh CSC–DC vaccination significantly inhibited tumor growth, reduced spontaneous lung metastases resulting in increased survival. CCR10 and its ligands were down-regulated on ALDHhigh D5 CSCs and in lung tissues respectively in animals subjected to ALDHhigh D5 CSC–DC vaccination. Down-regulation of CCR10 by siRNA significantly blocked tumor cell migration in vitro and metastasis in vivo. T cells harvested from ALDHhigh D5 CSC–DC vaccinated animals selectively killed the ALDHhigh D5 CSCs.  As a result, CSC-DC vaccination significantly decreased the percentage of ALDHhigh cells in residual tumors. These data indicate that, when used in an adjuvant setting, ALDHhigh CSC–DC vaccines effectively inhibit local tumor recurrence, reduce spontaneous lung metastasis, and prolong animal survival; compared with traditional DC vaccines and that simultaneous PD-L1 blockade can significantly enhance this effect.  This study has highlighted the potential application of cancer stem cell vaccine in clinical, particularly in the adjuvant setting.