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新发现为T细胞淋巴瘤治疗研究提供模型
作者:小柯机器人 发布时间:2019/8/26 15:33:55

法国蔚蓝海岸大学的Jean-Ehrland Ricci和Els Verhoeyen研究组合作发现,T细胞谱系中的GAPDH过表达通过NF-κB依赖性机制促进血管免疫母细胞性T细胞淋巴瘤的产生。2019年8月22日,《癌细胞》在线发表了这一成果。

GAPDH在T细胞发育和功能中发挥了关键性作用。为了研究GAPDH在T细胞中的作用,研究人员构建了在T细胞谱系中过表达GAPDH的转基因小鼠模型。老年小鼠形成外周Tfh样淋巴瘤,这涵盖了人血管免疫母细胞性T细胞淋巴瘤(AITL)的关键分子、病理和免疫表型特征。GAPDH在小鼠T细胞中诱导非经典NF-κB途径激活,这也在人AITL中强烈激活。

研究人员开发了一种NIK抑制剂,以揭示靶向NF-κB途径,从而可延长单独携带AITL的小鼠存活期并与抗PD-1组合。

这些发现提示了在AITL中靶向NF-κB信号通路的治疗潜力,并为将来的AITL治疗研究提供了模型。

附:英文原文

Title: GAPDH Overexpression in the T Cell Lineage Promotes Angioimmunoblastic T Cell Lymphoma through an NF-κB-Dependent Mechanism

Author: Laura Mondragón,Rana Mhaidly,Gian Marco De Donatis,Marie Tosolini,Pascal Dao,Anthony R. Martin,Caroline Pons,Johanna Chiche,Marie Jacquin,Véronique Imbert,Emma Proïcs,Laurent Boyer,Anne Doye,Frédéric Luciano,Jaap G. Neels,Frédéric Coutant,Nicole Fabien,Laura Sormani,Camila Rubio-Patiño,Jozef P. Bossowski,Florian Muller,Sandrine Marchetti,Elodie Villa,Jean-François Peyron,Philippe Gaulard,François Lemonnier,Vahid Asnafi,Laurent Genestier,Rachid Benhida,Jean-Jacques Fournié,Thierry Passeron,Jean-Ehrland Ricci,Els Verhoeyen

Issue&Volume: 22 August 2019

Abstract: GAPDH is emerging as a key player in T cell development and function. To investigate the role of GAPDH in T cells, we generated a transgenic mouse model overexpressing GAPDH in the T cell lineage. Aged mice developed a peripheral Tfh-like lymphoma that recapitulated key molecular, pathological, and immunophenotypic features of human angioimmunoblastic T cell lymphoma (AITL). GAPDH induced non-canonical NF-κB pathway activation in mouse T cells, which was strongly activated in human AITL. We developed a NIK inhibitor to reveal that targeting the NF-κB pathway prolonged AITL-bearing mouse survival alone and in combination with anti-PD-1. These findings suggest the therapeutic potential of targeting NF-κB signaling in AITL and provide a model for future AITL therapeutic investigations.

DOI: https://doi.org/10.1016/j.ccell.2019.07.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(19)30335-6

期刊信息

Cancer Cell:《癌细胞》,创刊于2002年。隶属于细胞出版社,最新IF:23.916
官方网址:https://www.cell.com/cancer-cell/home
投稿链接:https://www.editorialmanager.com/cancer-cell/default.aspx