Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines
Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines
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DOI：
10.1007/s00432-012-1311-2
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发表时间：
2013-01-01
影响因子：
3.6
通讯作者：
Albers, Andreas E.
中科院分区：
文献类型：
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作者：
Liao, Tian;Kaufmann, Andreas M.;Albers, Andreas E.
为了探讨肿瘤干细胞对宿主细胞毒性T淋巴细胞（CTL）介导的免疫应答的敏感性，我们比较了由肿瘤细胞系产生的假定CSC对同种抗原特异性CD 8（+）CTL的免疫识别和杀伤的敏感性。与单层来源的细胞（MDC）相比，CSC富集的球体培养来源的细胞（SDC）在所有研究的3种肿瘤细胞系上表现出更高的ALDH、ICAM 1和干/祖细胞标志物表达，而在宫颈癌细胞系上表现出更低的MHC I类分子表达。与匹配的MDC相比，CSC群体对MHC I类限制性同种异体抗原特异性CD 8（+）CTL裂解的敏感性较低。IFN-γ预处理导致SDC的过度比例增强的裂解。最后，ALDH（高）表达的SDC亚群比ALDH（低）表达的SDC对CD 8（+）CTL杀伤更敏感。我们显示CSC对CTL介导的裂解的体外易感性。因此，靶向ALDH（+）CSC的免疫治疗可能是一种有前途的方法。我们的研究结果和方法可能有助于佐剂的开发和优化，如本文所例示的INF-γ，用于CSC靶向疫苗，独立于CSC特异性抗原的可用性。
To explore cancer stem cell susceptibility to a host's cytotoxic T lymphocyte (CTL)-mediated immune response.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).The expression of ICAM1 and MHCI was upregulated by IFN-gamma treatment. CSC populations were less sensitive to MHC class I-restricted alloantigen-specific CD8(+) CTL lysis as compared to matched MDC. IFN-gamma pretreatment resulted in over-proportionally enhanced lysis of SDC. Finally, the subset of ALDH(high) expressing SDC presented more sensitivity toward CD8(+) CTL killing than the ALDH(low) SDC.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-gamma, for CSC-targeted vaccines, independent of the availability of CSC-specific antigens.