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

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@article{9fd9dbf371654059b9429b7ad2735246,
title = "T-cell number and subtype influence the disease course of primary chronic lymphocytic leukaemia xenografts in alymphoid mice",
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.",
keywords = "CLL, mouse model, T-cell depletion",
author = "Ceri Oldreive and Anna Skowronska and Nicholas Davies and Helen Parry and Angelo Agathanggelou and Sergey Krysov and Graham Packham and Zbigniew Rudzki and Laura Cronin and Katerina Vrzalikova and Paul Murray and Elena Odintsova and Guy Pratt and Malcolm Taylor and Paul Moss and Tatjana Stankovic",
year = "2015",
month = oct,
day = "28",
doi = "10.1242/dmm.021147",
language = "English",
volume = "8",
pages = "1401--1412",
journal = "Disease Models & Mechanisms",
issn = "1754-8403",
publisher = "The Company of Biologists Ltd.",

}

RIS

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 -