Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.
Dissecting the regulatory microenvironment of a large animal model of non-Hodgkin lymphoma: evidence of a negative prognostic impact of FOXP3+ T cells in canine B cell lymphoma.
复制标题
DOI：
10.1371/journal.pone.0105027
复制
发表时间：
2014
期刊：
影响因子：
3.7
通讯作者：
Garden OA
中科院分区：
文献类型：
--
作者：
Pinheiro D;Chang YM;Bryant H;Szladovits B;Dalessandri T;Davison LJ;Yallop E;Mills E;Leo C;Lara A;Stell A;Polton G;Garden OA
癌症微环境在肿瘤发生中起着关键作用，包含许多减弱抗肿瘤免疫反应的调节细胞。虽然调节性T细胞（Treg）在大多数实体组织肿瘤中的负面预后影响已得到充分证实，但它们在淋巴恶性肿瘤中的作用仍不清楚。在患有自发性多中心B细胞淋巴瘤（BCL）的狗的受影响淋巴结的细针抽吸物中记录了表达FOXP 3和Helios的T细胞，所述BCL被提议作为人非霍奇金淋巴瘤的模型。多变量分析显示，淋巴结FOXP 3 + T细胞的频率是一个独立的负面预后因素，当比较显示高于中值FOXP 3表达的狗与显示中值FOXP 3表达或更低的狗时，影响无进展生存期（危害比1.10; p = 0.01）和总生存期（危害比1.61; p = 0.01）。这些数据表明，在犬多中心BCL中存在类似于胸腺TCLs的TCLs群体，我们推测其被来自外周的肿瘤所吸收。我们认为，犬多中心BCL代表了一个强大的大型动物模型的人弥漫性大BCL，显示临床，细胞学和免疫表型的相似性，在人的疾病，允许免疫调节机制的比较研究。
The cancer microenvironment plays a pivotal role in oncogenesis, containing a number of regulatory cells that attenuate the anti-neoplastic immune response. While the negative prognostic impact of regulatory T cells (Tregs) in the context of most solid tissue tumors is well established, their role in lymphoid malignancies remains unclear. T cells expressing FOXP3 and Helios were documented in the fine needle aspirates of affected lymph nodes of dogs with spontaneous multicentric B cell lymphoma (BCL), proposed to be a model for human non-Hodgkin lymphoma. Multivariable analysis revealed that the frequency of lymph node FOXP3+ T cells was an independent negative prognostic factor, impacting both progression-free survival (hazard ratio 1.10; p = 0.01) and overall survival (hazard ratio 1.61; p = 0.01) when comparing dogs showing higher than the median FOXP3 expression with those showing the median value of FOXP3 expression or less. Taken together, these data suggest the existence of a population of Tregs operational in canine multicentric BCL that resembles thymic Tregs, which we speculate are co-opted by the tumor from the periphery. We suggest that canine multicentric BCL represents a robust large animal model of human diffuse large BCL, showing clinical, cytological and immunophenotypic similarities with the disease in man, allowing comparative studies of immunoregulatory mechanisms.
登录
查看更多内容
影响因子：
3.7
作者：
Akimova T;Beier UH;Wang L;Levine MH;Hancock WW
通讯作者：
Hancock WW
影响因子：
2.4
作者：
Fournel-Fleury, C;Ponce, F;Magnol, JP
通讯作者：
Magnol, JP
影响因子：
20.3
作者：
Carreras, Joaquim;Lopez-Guillermo, Armando;Banham, Alison H.
通讯作者：
Banham, Alison H.
影响因子：
2.1
作者：
Aresu, L.;Martini, V.;Marconato, L.
通讯作者：
Marconato, L.
影响因子：
6.5
作者：
Fujii, K;Ishimaru, F;Tanimoto, M
通讯作者：
Tanimoto, M