Follicular helper T-cells: expanding roles in T-cell lymphoma and targets for treatment
Follicular helper T-cells: expanding roles in T-cell lymphoma and targets for treatment
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DOI：
10.1111/bjh.12941
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发表时间：
2014-08-01
影响因子：
6.5
通讯作者：
Wagner, Simon D.
中科院分区：
文献类型：
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作者：
Ahearne, Matthew J.;Allchin, Rebecca L.;Wagner, Simon D.
滤泡辅助T细胞(TFH细胞)是CD4(+)T细胞的一个亚群，对于正常产生高亲和力抗体是必不可少的。TFH细胞特征性地产生IL21和IL4，并高表达表面标志CXCR5、ICOS、PDCD1(PD-1)和趋化因子CXCL13。在这篇综述中，我们将集中于TFH细胞与T细胞非霍奇金淋巴瘤亚型之间的新出现的联系：血管免疫母细胞T细胞淋巴瘤(AITL)和类似于20%的外周T细胞淋巴瘤(PTCL-NOS)具有TFH细胞的表面标志特征并共享一系列遗传异常。与AITL相关的反复发生的遗传异常包括表观遗传修饰物TET2和DNMT3A的突变，以及运动和黏附基因RHOA的突变，在高达70%的病例中。与20%的PTCL-NOS类似，显示RHOA突变，并具有其他特征，提示起源于TFH细胞。人们认识到特定的遗传和表面标记与恶性TFH细胞有关，这表明未来几年将在诊断和治疗可能性方面带来重大变化。例如，针对IL21、PDCD1和ICOS的抗体已经在针对自身免疫性疾病或其他恶性肿瘤的临床试验中，针对CXCL13的抗体正在临床前开发中。
Follicular helper T-cells (Tfh cells) are a subset of CD4(+) T-cells that are essential for normal production of high affinity antibodies. Tfh cells characteristically produce IL21 and IL4 and show high expression of surface markers CXCR5, ICOS, PDCD1 (PD-1) and the chemokine CXCL13. In this review we will focus on the emerging links between Tfh cells and subtypes of T-cell non-Hodgkin lymphoma: angioimmunoblastic T-cell lymphoma (AITL) and similar to 20% of peripheral T-cell lymphoma not otherwise specified (PTCL-NOS) have surface marker features of Tfh cells and share a spectrum of genetic abnormalities. The recurrent genetic abnormalities associated with AITL include mutations in epigenetic modifiers such as TET2 and DNMT3A and the motility and adhesion gene, RHOA, is mutated in up to 70% of cases. similar to 20% of PTCL-NOS demonstrate RHOA mutations and have other characteristics suggesting an origin in Tfh cells. The recognition that specific genetic and surface markers are associated with malignant Tfh cells suggests that the next few years will bring major changes in diagnostic and treatment possibilities. For example, antibodies against IL21, PDCD1 and ICOS are already in clinical trials for autoimmune disease or other malignancies and antibodies against CXCL13 are in pre-clinical development.