Abstract
Chronic lymphocytic leukaemia (CLL) cells require micorenvironmental support for their proliferation. This can be recapitulated in highly immunocompromised hosts in the presence of T-cells and other supporting cells. Current primary CLL xenograft models suffer from limited duration of tumour cell engraftment coupled with gradual T-cell outgrowth. Thus, a greater understanding of the interaction between CLL and T-cells could improve their utility. In this study, using two distinct xenograft models, we investigated whether xenografts recapitulate CLL biology including natural environmental interactions with B-cell receptors and T-cells and whether manipulation of autologous T-cells can expand the duration of CLL engraftment. We observed that primary CLL xenografts recapitulated both the tumour phenotype and T-cell repertoire observed in patients and that engraftment was significantly shorter for progressive tumours. Reduction of patients' T-cells to 2-5% of the initial T-cell number or specific depletion of CD8(+) cells extended the limited xenograft duration of progressive cases to that characteristic of indolent disease. We conclude that manipulation of T-cells can enhance current CLL xenograft models expanding their utility for investigation of tumour biology and pre-clinical drug assessment.
Original language | English |
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Pages (from-to) | 1401-1412 |
Number of pages | 12 |
Journal | Disease Models and Mechanisms |
Volume | 8 |
Early online date | 20 Aug 2015 |
DOIs | |
Publication status | Published - 28 Oct 2015 |
Keywords
- CLL
- mouse model
- T-cell depletion
ASJC Scopus subject areas
- Cancer Research