Shatnyeva Olga M, Hansen Hinrich P, Reiners Katrin S, Sauer Maike, Vyas Maulik, von Strandmann Elke Pogge
Innate Immunity Group, Clinic 1 for Internal Medicine, University of Cologne , Cologne, Germany.
Front Genet. 2015 Feb 4;6:11. doi: 10.3389/fgene.2015.00011. eCollection 2015.
Chronic lymphocytic leukemia (CLL) is the most prominent B cell malignancy among adults in the Western world and characterized by a clonal expansion of B cells. The patients suffer from severe immune defects resulting in increased susceptibility to infections and failure to generate an antitumor immune response. Defects in both, DNA damage response (DDR) pathway and crosstalk with the tissue microenvironment have been reported to play a crucial role for the survival of CLL cells, therapy resistance and impaired immune response. To this end, major advances over the past years have highlighted several T cell immune evasion mechanisms in CLL. Here, we discuss the consequences of an impaired DDR pathway for detection and elimination of CLL cells by natural killer (NK) cells. NK cells are considered to be a major component of the immunosurveillance in leukemia but NK cell activity is impaired in CLL. Restoration of NK cell activity using immunoligands and immunoconstructs in combination with the conventional chemotherapy may provide a future perspective for CLL treatment.
慢性淋巴细胞白血病（CLL）是西方世界成年人中最常见的B细胞恶性肿瘤，其特征是B细胞的克隆性扩增。患者存在严重的免疫缺陷，导致对感染的易感性增加，且无法产生抗肿瘤免疫反应。据报道，DNA损伤反应（DDR）途径的缺陷以及与组织微环境的相互作用在CLL细胞的存活、治疗耐药性和免疫反应受损中起着关键作用。为此，过去几年的重大进展突出了CLL中的几种T细胞免疫逃逸机制。在这里，我们讨论DDR途径受损对自然杀伤（NK）细胞检测和清除CLL细胞的影响。NK细胞被认为是白血病免疫监视的主要组成部分，但CLL患者的NK细胞活性受损。使用免疫配体和免疫构建体结合传统化疗恢复NK细胞活性可能为CLL治疗提供未来前景。
