期刊
ONCOIMMUNOLOGY
卷 4, 期 3, 页码 -出版社
TAYLOR & FRANCIS INC
DOI: 10.4161/2162402X.2014.990767
关键词
antitumor immunity; cancer stem cell; dendritic cell; metastasis; vaccine
资金
- Elsa U. Pardee Foundation
- Gillson Longenbaugh Foundation
- Science and Technology Program of Guangdong, China [2012A0304000590]
- Science and Technology Program of Guangzhou, China [2013J4500005]
- National Science Fund of China [30971112]
The inability to target cancer stem cells (CSC) may be a significant factor contributing to treatment failure. We have developed a strategy to target the CSC populations in melanoma and squamous cell carcinoma using CSC lysate-pulsed dendritic cells (DCs). The CSC-DC vaccine was administered in the adjuvant setting after localized radiation therapy of established tumors. Using mouse models we demonstrated that DCs pulsed with CSCs enriched by virtue of their expression of the CSC marker ALDH (termed CSC-DC) significantly inhibited tumor growth, reduced development of pulmonary metastases and prolonged survival. The effect was associated with downregulation of chemokine (C-C motif) receptors CCR7 and CCR10 in tumor cells and decreased expression of the chemokine (C-C motif) ligands CCL21, CCL27 and CCL28 in lung tissue. The CSC-DC vaccine significantly reduced ALDH(high) CSC frequency in primary tumors. Direct targeting of CSCs was demonstrated by the specific binding of IgG produced by ALDH(high) CSC-DC vaccine-primed B cells to ALDH(high) CSCs, resulting in lysis of these target CSCs in the presence of complement. These data suggest that the CSC-DC vaccine approach may be useful in the adjuvant setting where local and systemic relapse are high after conventional treatment of cancers.
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