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The activity of γδ T cells against paediatric liver tumour cells and spheroids in cell culture
Author(s) -
Hoh Alexander,
Dewerth Alexander,
Vogt Fabian,
Wenz Julia,
Baeuerle Patrick A.,
Warmann Steven W.,
Fuchs Joerg,
ArmeanuEbinger Sorin
Publication year - 2013
Publication title -
liver international
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.873
H-Index - 110
eISSN - 1478-3231
pISSN - 1478-3223
DOI - 10.1111/liv.12011
Subject(s) - cytotoxic t cell , cancer research , cell culture , immune system , hepatoblastoma , transplantation , cytotoxicity , viability assay , t cell , bone marrow , cell , immunology , biology , medicine , in vitro , biochemistry , genetics
Abstract Background Chemoresistance and advanced tumour stage at time of diagnosis are the major reasons for poor treatment results in hepatoblastoma ( HB ) and paediatric hepatocellular carcinoma ( HCC ). Positive results with transplantation of liver and bone marrow revealed the impact of the immune system on the treatment of liver malignancies. Aim Cytotoxic‐immune‐cells‐like natural killer ( NK ) and T cells are major player in the defence against developing tumours. This study aimed to specifically analyse the ability of ex‐vivo expanded γδ T cells to recognise and lyse HB and HCC cell lines in coculture assays. Methods Cell viability after treatment with γδ T cells was evaluated with two HB ( HUH 6 and HepT1) and one HCC cell line ( HC ‐ AFW 1) using a MTT ‐based cytotoxicity assay. The binding of T cells to target cells was monitored using immunofluorescence microscopy. Results Incubation of hepatic tumour cell lines with γδ T cells led to a significant decrease in tumour cell viability. This was enhanced by zoledronic acid and histone deacetylase inhibitors. MT 110, an Ep CAM / CD 3‐bispecific Bi TE antibody could bluntly enhance tumour cell lysis close to completion. γδ T cells efficiently interacted with HB and HCC cells in a spheroid culture model. Conclusion Bispecific antibodies such as MT 110 might be used to intensify the antitumoural effect of γδ T cells in context of adoptive immune cell transfer. Optimised immunotherapeutic strategies might therefore improve the outcome of high risk hepatoblastoma and hepatocellular carcinoma.