title: Susceptibility to cytotoxic T cell lysis of cancer stem cells derived from cervical and head and neck tumor cell lines.
abstract: OBJECTIVE
  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 ALDH(high) expressing SDC presented more sensitivity toward CD8(+) CTL killing than the ALDH(low) 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.
authors.affiliation: Clinic for Gynecology, Charité-Universitätsmedizin Berlin, 12200 Berlin, Germany.
authors.forename: Tian
authors.initials: T
authors.lastname: Liao
authors.forename: Andreas M
authors.initials: AM
authors.lastname: Kaufmann
authors.forename: Xu
authors.initials: X
authors.lastname: Qian
authors.forename: Voramon
authors.initials: V
authors.lastname: Sangvatanakul
authors.forename: Chao
authors.initials: C
authors.lastname: Chen
authors.forename: Tina
authors.initials: T
authors.lastname: Kube
authors.forename: Guoyou
authors.initials: G
authors.lastname: Zhang
authors.forename: Andreas E
authors.initials: AE
authors.lastname: Albers
mesh_terms: D000080924:Aldehyde Dehydrogenase 1 Family; D018122:B7-1 Antigen / Q000032:analysis; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology*; D002294:Carcinoma, Squamous Cell / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D045744:Cell Line, Tumor / Q000276:immunology; D003602:Cytotoxicity, Immunologic; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D005805:Genes, MHC Class I; D005802:Genes, MHC Class II; D006258:Head and Neck Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*; D018398:Homeodomain Proteins / Q000378:metabolism; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000378:metabolism; D007371:Interferon-gamma / Q000494:pharmacology; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D000071317:Nanog Homeobox Protein; D014411:Neoplastic Stem Cells / Q000276:immunology*; D050814:Octamer Transcription Factor-3 / Q000378:metabolism; D050697:Retinal Dehydrogenase / Q000378:metabolism; D055748:SOXB1 Transcription Factors / Q000378:metabolism; D018874:Spheroids, Cellular; D013602:T-Lymphocytes, Cytotoxic / Q000276:immunology*; D002583:Uterine Cervical Neoplasms / Q000276:immunology* / Q000473:pathology / Q000628:therapy*
chemical_list: D018122:B7-1 Antigen; D018398:Homeodomain Proteins; C573420:ICAM1 protein, human; D007527:Isoenzymes; C486780:NANOG protein, human; D000071317:Nanog Homeobox Protein; D050814:Octamer Transcription Factor-3; C494173:POU5F1 protein, human; C527782:SOX2 protein, human; D055748:SOXB1 Transcription Factors; D018799:Intercellular Adhesion Molecule-1; D007371:Interferon-gamma; D000080924:Aldehyde Dehydrogenase 1 Family; C510223:ALDH1A1 protein, human; D050697:Retinal Dehydrogenase