Immunobiological characterization of cancer stem cells isolated from glioblastoma patients

Tiziano Di Tomaso, Stefania Mazzoleni, Ena Wang, Gloria Sovena, Daniela Clavenna, Alberto Franzin, Pietro Mortini, Soldano Ferrone, Claudio Doglioni, Francesco M. Marincola, Rossella Galli, Giorgio Parmiani, Cristina Maccalli

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Abstract

Purpose: Cancer stem cells (CSC) have been isolated from human tumors, including glioblastoma multiforme (GBM). The aims of this study were the immunobiological characterization of GBM CSCs and the assessment of whether these cells represent suitable targets for immunotherapy. Experimental Design: GBM CSC lines and their fetal bovine serum (FBS)-cultured non-CSC pair lines were generated and examined by flow cytometry for expression of known tumor antigens, MHC-I and MHC-II molecules, antigen-processing machinery components, and NKG2D ligands. In addition, immunogenicity and immunosuppression of such cell lines for autologous or allogeneic T lymphocytes were tested by cytokine secretion (ELISPOT) or proliferation (carboxyfluorescein diacetate succinimidyl ester) assays, respectively. Results: Both GBM CSC and FBS lines were weakly positive and negative for MHC-I, MHC-II, and NKG2D ligand molecules, respectively. Antigen-processing machinery molecules were also defective in both cell types. Upregulation of most molecules was induced by IFNs or 5-Aza deoxycytidine, although more efficiently in FBS than in CSCs. Patient T-cell responses, mediated by both TH1 and the TH2 subsets, against autologous CSC could be induced in vitro. In addition, CSC but not their paired FBS tumor lines inhibited T-cell proliferation of healthy donors. Notably, a differential gene signature that was confirmed at the protein levels for some immunologic-related molecules was also found between CSC and FBS lines. Conclusions: These results indicate lower immunogenicity and higher suppressive activity of GBM CSC compared with FBS lines. The immunogenicity, however, could be rescued by immune modulation leading to anti-GBM T cell-mediated immune response.

Original languageEnglish
Pages (from-to)800-813
Number of pages14
JournalClinical Cancer Research
Volume16
Issue number3
DOIs
Publication statusPublished - 1 Feb 2010

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ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Di Tomaso, T., Mazzoleni, S., Wang, E., Sovena, G., Clavenna, D., Franzin, A., Mortini, P., Ferrone, S., Doglioni, C., Marincola, F. M., Galli, R., Parmiani, G., & Maccalli, C. (2010). Immunobiological characterization of cancer stem cells isolated from glioblastoma patients. Clinical Cancer Research, 16(3), 800-813. https://doi.org/10.1158/1078-0432.CCR-09-2730