title: Cancer stem cell vaccine inhibits metastases of primary tumors and induces humoral immune responses against cancer stem cells.
abstract: 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 ALDHhighCSC frequency in primary tumors. Direct targeting of CSCs was demonstrated by the specific binding of IgG produced by ALDHhighCSC-DC vaccine-primed B cells to ALDHhighCSCs, 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.
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA ; State Key Laboratory of Oncology in Southern China and Department of Experimental Research; Sun Yat-sen University Cancer Center ; Guangzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Lu
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA ; Center for Stem Cell Research and Application; Institute of Hematology; Union Hospital, Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan, China.
authors.forename: Huimin
authors.initials: H
authors.lastname: Tao
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: Alfred E
authors.initials: AE
authors.lastname: Chang
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA ; Center for Stem Cell Research and Application; Institute of Hematology; Union Hospital, Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan, China.
authors.forename: Yangyang
authors.initials: Y
authors.lastname: Hu
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA ; Second Xiangya Hospital; Central South University ; Changsha, Hunan, China.
authors.forename: Guoshun
authors.initials: G
authors.lastname: Shu
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA ; Department of General Surgery; Tongji Hospital of Tongji University ; Shanghai, China.
authors.forename: Quanning
authors.initials: Q
authors.lastname: Chen
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: Martin
authors.initials: M
authors.lastname: Egenti
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: John
authors.initials: J
authors.lastname: Owen
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: Jeffrey S
authors.initials: JS
authors.lastname: Moyer
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: Mark Ep
authors.initials: ME
authors.lastname: Prince
authors.affiliation: Center for Stem Cell Research and Application; Institute of Hematology; Union Hospital, Tongji Medical College ; Huazhong University of Science and Technology ; Wuhan, China.
authors.forename: Shiang
authors.initials: S
authors.lastname: Huang
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: Max S
authors.initials: MS
authors.lastname: Wicha
authors.affiliation: State Key Laboratory of Oncology in Southern China and Department of Experimental Research; Sun Yat-sen University Cancer Center ; Guangzhou, China.
authors.forename: Jian-Chuan
authors.initials: JC
authors.lastname: Xia
authors.affiliation: University of Michigan Comprehensive Cancer Cente; Ann Arbor , MI USA.
authors.forename: Qiao
authors.initials: Q
authors.lastname: Li
keywords: ALDH, aldehyde dehydrogenase; CSC, cancer stem cell; CSC-DC, CSC lysate-pulsed dendritic cell; DC, dendritic cell; H-DC; RT, radiation therapy; antitumor immunity; cancer stem cell; dendritic cell; heterogeneous; metastasis; qRT-PCR, real time quantitative PCR; unsorted tumor cell lysate-pulsed dendritic cell; vaccine