T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice

Research output: Contribution to journalArticle

External organisations

  • University of Southampton

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.

Details

Original languageEnglish
Pages (from-to)1401-1412
Number of pages12
JournalDisease Models and Mechanisms
Volume8
Early online date20 Aug 2015
Publication statusPublished - 28 Oct 2015

Keywords

  • CLL, mouse model, T-cell depletion

ASJC Scopus subject areas