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依鲁替尼和idelalisib可阻断与慢性淋巴细胞白血病(CLL)细胞在肿瘤微环境中的黏附和激活相关的免疫表型变化。

Ibrutinib and idelalisib block immunophenotypic changes associated with the adhesion and activation of CLL cells in the tumor microenvironment.

作者信息

Shen Yandong, Best O Giles, Mulligan Stephen P, Christopherson Richard I

机构信息

a School of Life and Environmental Sciences , University of Sydney , Sydney , Australia.

b Northern Blood Research Centre , Kolling Institute of Medical Research , St Leonards , Australia.

出版信息

Leuk Lymphoma. 2018 Aug;59(8):1927-1937. doi: 10.1080/10428194.2017.1403598. Epub 2017 Nov 22.

DOI:10.1080/10428194.2017.1403598
PMID:29164976
Abstract

The lymph node and bone marrow microenvironments promote the survival and proliferation of CLL cells. Defining the immunophenotype of CLL cells from the tumor microenvironment may help to better understand the mechanisms of action of current therapies and identify novel drug targets. Significant changes in the levels of 25 CD antigens were identified using the DotScan™ antibody microarray following CLL-cell culture with CD40L-expressing fibroblasts. Ibrutinib or idelalisib countered the change in expression of 11 of these antigens (CD23, CD27, CD53, CD58, CD71, CD80, CD84, CD97, CD126, CD150, and FMC7), which have known roles in cell activation and adhesion. The immunophenotypic changes identified may provide further insight into the mechanisms by which CLL cells interact with the tumor microenvironment and better define how ibrutinib and idelalisib release CLL cells from the lymph nodes and bone marrow.

摘要

淋巴结和骨髓微环境促进慢性淋巴细胞白血病(CLL)细胞的存活和增殖。定义来自肿瘤微环境的CLL细胞的免疫表型可能有助于更好地理解当前疗法的作用机制并识别新的药物靶点。在用表达CD40L的成纤维细胞培养CLL细胞后,使用DotScan™抗体微阵列鉴定了25种CD抗原水平的显著变化。依鲁替尼或idelalisib对抗了其中11种抗原(CD23、CD27、CD53、CD58、CD71、CD80、CD84、CD97、CD126、CD150和FMC7)表达的变化,这些抗原在细胞活化和黏附中具有已知作用。所确定的免疫表型变化可能会进一步深入了解CLL细胞与肿瘤微环境相互作用的机制,并更好地定义依鲁替尼和idelalisib如何将CLL细胞从淋巴结和骨髓中释放出来。

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