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Clinical & Experimental Metastasis
Published in: Clinical & Experimental Metastasis 6/2013

01-08-2013 | Research Paper

Characterization of small spheres derived from various solid tumor cell lines: are they suitable targets for T cells?

Authors: Antonia Busse, Anne Letsch, Alberto Fusi, Anika Nonnenmacher, David Stather, Sebastian Ochsenreither, Christian RA Regenbrecht, Ulrich Keilholz

Published in: Clinical & Experimental Metastasis | Issue 6/2013

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Abstract

T cell based immunotherapy has been investigated in a variety of malignancies and analyses have been mostly founded on in vitro data with tumor cell monolayers. However, three-dimensional (3D) culture models might mimic more closely the ‘in vivo’ conditions than 2D monolayers. Therefore, we analyzed the expression of tumor-associated antigens (TAA) and of molecules involved in antigen processing and presentation (APM) in tumor spheres, which served as an in vitro model for micrometastasis which might be enriched in tumor propagating cancer stem cells. For enrichment of sphere cells 12 human solid tumor cell lines were cultured in serum-free medium. Expression of a variety of TAA and APM were analyzed by RT-PCR and/or flow cytometry and compared to expression in corresponding adherent bulk cells grown in regular growth medium. Compared to adherent cells, spheres showed equal or higher mRNA expression levels of LMP2, LMP7 and MECL-1, of TAP1 and TAP2 transporters and, surprisingly, also of TAA including differentiation antigens. However, downregulation or loss of HLA-I and HLA-II molecules in spheres was observed in 8 of 10 and 1 of 2 cell lines, respectively, and was unresponsive to stimulation with IFN-γ. Although tumor spheres express TAA and molecules of intracellular antigen processing, they are defective in antigen presentation due to downregulation of HLA surface expression which may lead to immune evasion.
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Metadata
Title
Characterization of small spheres derived from various solid tumor cell lines: are they suitable targets for T cells?
Authors
Antonia Busse
Anne Letsch
Alberto Fusi
Anika Nonnenmacher
David Stather
Sebastian Ochsenreither
Christian RA Regenbrecht
Ulrich Keilholz
Publication date
01-08-2013
Publisher
Springer Netherlands
Published in
Clinical & Experimental Metastasis / Issue 6/2013
Print ISSN: 0262-0898
Electronic ISSN: 1573-7276
DOI
https://doi.org/10.1007/s10585-013-9578-5

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