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首页> 外文期刊>British Journal of Cancer >HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma
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HLA class I is most tightly linked to levels of tapasin compared with other antigen-processing proteins in glioblastoma

机译：与胶质母细胞瘤中的其他抗原加工蛋白相比，HLA I类与塔帕森蛋白酶的水平联系最紧密

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Background: Tumour cells can evade the immune system by dysregulation of human leukocyte antigens (HLA-I). Low quantity and/or altered quality of HLA-I cell surface expression is the result of either HLA-I alterations or dysregulations of proteins of the antigen-processing machinery (APM). Tapasin is an APM protein dedicated to the maturation of HLA-I and dysregulation of tapasin has been linked to higher malignancy in several different tumours. Methods: We studied the expression of APM components and HLA-I, as well as HLA-I tapasin-dependency profiles in glioblastoma tissues and corresponding cell lines. Results: Tapasin displayed the strongest correlation to HLA-I heavy chain but also clustered with β _(2)-microglobulin, transporter associated with antigen processing (TAP) and LMP. Moreover, tapasin also correlated to survival of glioblastoma patients. Some APM components, for example, TAP1/TAP2 and LMP2/LMP7, showed variable but coordinated expression, whereas ERAP1/ERAP2 displayed an imbalanced expression pattern. Furthermore, analysis of HLA-I profiles revealed variable tapasin dependence of HLA-I allomorphs in glioblastoma patients. Conclusions: Expression of APM proteins is highly variable between glioblastomas. Tapasin stands out as the APM component strongest correlated to HLA-I expression and we proved that HLA-I profiles in glioblastoma patients include tapasin-dependent allomorphs. The level of tapasin was also correlated with patient survival time. Our results support the need for individualisation of immunotherapy protocols.
机译：背景：肿瘤细胞可通过人类白细胞抗原（HLA-1）失调来逃避免疫系统。 HLA-1细胞表面表达的数量低和/或质量改变是抗原加工机器（APM）的蛋白质的HLA-1改变或失调的结果。 Tapasin是一种APM蛋白，专门用于HLA-1的成熟，并且Tapasin的失调与几种不同肿瘤中较高的恶性肿瘤有关。方法：我们研究了胶质母细胞瘤组织和相应细胞系中APM成分和HLA-1的表达以及HLA-1胰蛋白酶的依赖性。结果：Tapasin显示与HLA-1重链最强的相关性，但也聚集了β_（2）-微球蛋白，与抗原加工（TAP）和LMP相关的转运蛋白。此外，胰蛋白酶也与胶质母细胞瘤患者的存活相关。某些APM组件，例如TAP1 / TAP2和LMP2 / LMP7，显示了可变但协调的表达，而ERAP1 / ERAP2显示了不平衡的表达模式。此外，对HLA-1谱的分析揭示了胶质母细胞瘤患者中HLA-1同种异形物对塔帕蛋白酶的依赖性。结论：胶质母细胞瘤之间APM蛋白的表达高度可变。 Tapasin是与HLA-1表达最相关的APM组分，因此我们脱颖而出，并且我们证明了胶质母细胞瘤患者的HLA-1概况包括Tapasin依赖性同种异体。胰蛋白酶的水平也与患者的生存时间相关。我们的结果支持对免疫疗法方案进行个性化的需求。

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