Artikel
Immunologic targeting of cancer stem cells
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Veröffentlicht: | 19. April 2011 |
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Gliederung
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Tumor recurrence has been attributed to a subset of tumor cells, called cancer stem cells (CSCs), which are more resistant to the effect of established treatments such as chemotherapy or radiation. One novel approach is T cell-mediated antitumor immunotherapy targeting these CSCs. However, the key point is that their sensitivity to the host’s cytotoxic T lymphocyte (CTL)-mediated immune response is still obscure. In this study, we investigated 3D-cultures (“spheroids”) enriched for CSC-like cells from head and neck cancer and cervical cancer cell lines and investigated their susceptibility to allogeneic tumor antigen-specific CD8+ CTL lysis. To characterize these cultures we determined expression of aldehyde dehydrogenase 1 (ALDH1) (28% in spheroids vs. <1% in monolayer) and other stem/progenitor cell markers (SOX2, Oct-4, Nanog). As compared to more “differentiated” monolayer-derived tumor cells, they expressed lower levels of MHC I but higher levels of ICAM-1 (P<0.05). These expression levels could be upregulated by interferon-γ (IFN-γ) treatment. Furthermore, CSC-like cells were less sensitive to MHC I-restricted CD8+ CTL-mediated cytotoxicity compared to non-CSC-like cells and there was no change in killing when they were pretreated with IFN-γ (P<0.05). Finally, we compared killing of ALDH1-positive cancer stem cell-like spheroid-derived cells to the ALDH1-negative cell population by allo-antigen specific CD8+ CTLs. The interaction between CSC and the human immune system may provide a basis for developing CTL-based antitumor vaccines targeting CSCs to eliminate specifically this tumor population, and thereby decrease recurrence and enhance patient’s long-term survival.