Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis
Invariant NKT cells contribute to chronic lymphocytic leukemia surveillance and prognosis
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DOI：
10.1182/blood-2016-11-751065
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发表时间：
2017-06-29
期刊：
影响因子：
20.3
通讯作者：
de Lalla, Claudia
中科院分区：
文献类型：
--
作者：
Gorini, Francesca;Azzimonti, Laura;de Lalla, Claudia
慢性淋巴细胞白血病（CLL）的特征是恶性CD 5（+）B淋巴细胞在血液、骨髓和淋巴器官中的扩增。CD 1d限制性不变自然杀伤T（iNKT）细胞是与肿瘤监视密切相关的先天性T淋巴细胞。我们在E mu-Tcl 1（Tcl 1）CLL小鼠模型和68例CLL患者中研究了iNKT细胞对疾病自然史的影响。我们发现Tcl 1-CLL细胞表达CD 1d，iNKT细胞严重延迟疾病发作，但在疾病进展时功能受损。在患者中，疾病进展与CLL细胞和受损iNKT细胞上的高CD 1d表达相关。相反，疾病稳定性与CLL细胞和正常iNKT细胞上的阴性或低CD 1d表达相关，表明间接的白血病控制。iNKT细胞确实通过抑制表达CD 1d的nurse样细胞（一种相关的前白血病巨噬细胞群体）在体外阻碍CLL存活。多变量分析确定iNKT细胞频率是疾病进展的独立预测因素。总之，这些结果支持了iNKT细胞对CLL免疫监视的贡献，并强调了iNKT细胞频率作为疾病进展的预后标志物。
Chronic lymphocytic leukemia (CLL) is characterized by the expansion of malignant CD5(+) B lymphocytes in blood, bone marrow, and lymphoid organs. CD1d-restricted invariant natural killer T (iNKT) cells are innate-like T lymphocytes strongly implicated in tumor surveillance. We investigated the impact of iNKT cells in the natural history of the disease in the E mu-Tcl1 (Tcl1) CLL mouse model and 68 CLL patients. We found that Tcl1-CLL cells express CD1d and that iNKT cells critically delay disease onset but become functionally impaired upon disease progression. In patients, disease progression correlates with high CD1d expression on CLL cells and impaired iNKT cells. Conversely, disease stability correlates with negative or low CD1d expression on CLL cells and normal iNKT cells, suggesting indirect leukemia control. iNKT cells indeed hinder CLL survival in vitro by restraining CD1d-expressing nurse-like cells, a relevant proleukemia macrophage population. Multivariable analysis identified iNKT cell frequency as an independent predictor of disease progression. Together, these results support the contribution of iNKT cells to CLL immune surveillance and highlight iNKT cell frequency as a prognostic marker for disease progression.