EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia.
EOMES is essential for antitumor activity of CD8(+) T cells in chronic lymphocytic leukemia.
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EOMES对于慢性淋巴细胞性白血病中CD8（+）T细胞的抗肿瘤活性至关重要。
DOI：
10.1038/s41375-021-01198-1
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发表时间：
2021-11
期刊：
影响因子：
11.4
通讯作者：
Seiffert M
中科院分区：
文献类型：
--
作者：
Llaó-Cid L;Roessner PM;Chapaprieta V;Öztürk S;Roider T;Bordas M;Izcue A;Colomer D;Dietrich S;Stilgenbauer S;Hanna B;Martín-Subero JI;Seiffert M
全基因组关联研究发现，影响转录因子Eomesodermin（EOMES）的单核苷酸多态性（SNP）与慢性淋巴细胞白血病（CLL）发生风险显著增加相关。表观遗传学分析、RNA测序和流式细胞术显示，EOMES不在CLL细胞中表达，但在CD 8 + T细胞中表达，EOMES是其已知的主调节因子。因此，我们假设与EOMES SNP相关的CLL风险增加可能是由其对CD 8 + T细胞介导的CLL免疫控制的负面影响来解释的。流式细胞术分析显示，与健康个体相比，CLL患者的CD 8 + T细胞中的EOMES表达更高，并且在CLL中，PD-1+ EOMES+ CD 8 + T细胞在淋巴结而不是血液或骨髓中积累。这与在白血病Eµ-TCL 1小鼠脾脏中观察到的EOMES+ CD 8 + T细胞扩增一致。由于EOMES表达在表达抑制性受体的CD 8 + T细胞中最高，因此EOMES参与T细胞耗竭和功能障碍似乎是可能的。有趣的是，CD 8 + T细胞中的Eomes缺陷导致其扩增受损，与小鼠中CLL控制降低相关。总体而言，这些观察结果表明，EOMES对于CD 8 + T细胞扩增和/或维持是必不可少的，因此参与CLL的适应性免疫控制。
Genome-wide association studies identified a single-nucleotide polymorphism (SNP) affecting the transcription factor Eomesodermin (EOMES) associated with a significantly increased risk to develop chronic lymphocytic leukemia (CLL). Epigenetic analyses, RNA sequencing, and flow cytometry revealed that EOMES is not expressed in CLL cells, but in CD8+ T cells for which EOMES is a known master regulator. We thus hypothesized that the increased CLL risk associated with the EOMES SNP might be explained by its negative impact on CD8+ T-cell-mediated immune control of CLL. Flow cytometry analyses revealed a higher EOMES expression in CD8+ T cells of CLL patients compared to healthy individuals, and an accumulation of PD-1+ EOMES+ CD8+ T cells in lymph nodes rather than blood or bone marrow in CLL. This was in line with an observed expansion of EOMES+ CD8+ T cells in the spleen of leukemic Eµ-TCL1 mice. As EOMES expression was highest in CD8+ T cells that express inhibitory receptors, an involvement of EOMES in T-cell exhaustion and dysfunction seems likely. Interestingly, Eomes-deficiency in CD8+ T cells resulted in their impaired expansion associated with decreased CLL control in mice. Overall, these observations suggest that EOMES is essential for CD8+ T-cell expansion and/or maintenance, and therefore involved in adaptive immune control of CLL.
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影响因子：
16.6
作者：
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影响因子：
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影响因子：
20.3
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通讯作者：
Gribben, John G.
影响因子：
11.4
作者：
Hanna, B. S.;McClanahan, F.;Seiffert, M.
通讯作者：
Seiffert, M.
影响因子：
20.3
作者：
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通讯作者：
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