T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice
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T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice. / Oldreive, Ceri; Skowronska, Anna; Davies, Nicholas; Parry, Helen; Agathanggelou, Angelo; Krysov, Sergey; Packham, Graham; Rudzki, Zbigniew; Cronin, Laura; Vrzalikova, Katerina; Murray, Paul; Odintsova, Elena; Pratt, Guy; Taylor, Malcolm; Moss, Paul; Stankovic, Tatjana.
In: Disease Models and Mechanisms, Vol. 8, 28.10.2015, p. 1401-1412.Research output: Contribution to journal › Article › peer-review
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TY - JOUR
T1 - T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice
AU - Oldreive, Ceri
AU - Skowronska, Anna
AU - Davies, Nicholas
AU - Parry, Helen
AU - Agathanggelou, Angelo
AU - Krysov, Sergey
AU - Packham, Graham
AU - Rudzki, Zbigniew
AU - Cronin, Laura
AU - Vrzalikova, Katerina
AU - Murray, Paul
AU - Odintsova, Elena
AU - Pratt, Guy
AU - Taylor, Malcolm
AU - Moss, Paul
AU - Stankovic, Tatjana
PY - 2015/10/28
Y1 - 2015/10/28
N2 - 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.
AB - 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.
KW - CLL
KW - mouse model
KW - T-cell depletion
U2 - 10.1242/dmm.021147
DO - 10.1242/dmm.021147
M3 - Article
C2 - 26398941
VL - 8
SP - 1401
EP - 1412
JO - Disease Models & Mechanisms
JF - Disease Models & Mechanisms
SN - 1754-8403
ER -