Erschienen in:
01.01.2013 | Original Paper
Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines
verfasst von:
Tian Liao, Andreas M. Kaufmann, Xu Qian, Voramon Sangvatanakul, Chao Chen, Tina Kube, Guoyou Zhang, Andreas E. Albers
Erschienen in:
Journal of Cancer Research and Clinical Oncology
|
Ausgabe 1/2013
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Abstract
Purpose
To explore cancer stem cell susceptibility to a host’s cytotoxic T lymphocyte (CTL)-mediated immune response.
Methods
We compared the susceptibility of putative CSC generated from cancer cell lines to immunologic recognition and killing by alloantigen-specific CD8+ CTL. CSC-enriched spheroid culture-derived cells (SDC) exhibited higher expression of ALDH, ICAM1 and of stem/progenitor cell markers on all 3 tumor cell lines investigated and lower MHC class I on the cervical cancer cell line as compared to their monolayer-derived cells (MDC).
Results
The expression of ICAM1 and MHCI was upregulated by IFN-γ treatment. CSC populations were less sensitive to MHC class I-restricted alloantigen-specific CD8+ CTL lysis as compared to matched MDC. IFN-γ pretreatment resulted in over-proportionally enhanced lysis of SDC. Finally, the subset of ALDHhigh expressing SDC presented more sensitivity toward CD8+ CTL killing than the ALDHlow SDC.
Conclusions
Tumor therapy resistance has been attributed to cancer stem cells (CSC). We show in vitro susceptibility of CSC to CTL-mediated lysis. Immunotherapy targeting of ALDH+ CSC may therefore be a promising approach. Our results and method may be helpful for the development and optimization of adjuvants, as here exemplified for INF-γ, for CSC-targeted vaccines, independent of the availability of CSC-specific antigens.