葡萄糖剥夺的肿瘤微环境激活 AMP 活化蛋白激酶驱动过继转移的 T 辅助 9 细胞衰老
Glucose-deprived tumor microenvironment activates AMP-activated protein kinase to drive adoptively transferred T helper 9 cell senescence.
辅助性T细胞9(Th9)细胞在针对实体瘤的过继细胞治疗(ACT)中显示出前景。
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:NK cell expansion requires HuR and mediates control of solid tumors and long-term virus infection.
NK cell expansion requires HuR and mediates control of solid tumors and long-term virus infection.
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自然杀伤(NK)细胞是一类能够通过直接裂解和产生细胞因子来控制肿瘤和病毒感染的淋巴细胞。虽然T细胞和NK细胞均可在受累组织中扩增和积聚,但NK细胞扩增在肿瘤和病毒控制中的作用尚不明确。在此,我们发现RNA结合蛋白HuR介导的转录后调控对NK细胞扩增至关重要,且不影响其效应功能。HuR缺陷的NK细胞在细胞周期中期表现出缺陷,包括Ska2表达下降和可变剪接异常,Ska2是纺锤体和动粒复合体的组成部分。HuR依赖的NK细胞扩增有助于长期巨细胞病毒控制,并在两种独立的肿瘤模型中促进皮下肿瘤的控制,但不影响肿瘤转移。这些结果表明,HuR介导的转录后调控特异性影响NK细胞扩增,而NK细胞扩增是长期病毒感染和实体瘤控制所必需的,但对急性感染或肿瘤转移则非必需,这突显了其与抗原特异性T细胞控制之间的根本差异。
Natural killer (NK) cells are lymphocytes capable of controlling tumors and virus infections through direct lysis and cytokine production. While both T and NK cells expand and accumulate in affected tissues, the role of NK cell expansion in tumor and viral control is not well understood.
Here, we show that posttranscriptional regulation by the RNA-binding protein HuR is essential for NK cell expansion without negatively affecting effector functions. HuR-deficient NK cells displayed defects in the metaphase of the cell cycle, including decreased expression and alternative splicing of Ska2, a component of the spindle and kinetochore complex.
HuR-dependent NK cell expansion contributed to long-term cytomegalovirus control and facilitated control of subcutaneous tumors but not tumor metastases in two independent tumor models. These results show that posttranscriptional regulation by HuR specifically affects NK cell expansion, which is required for the control of long-term virus infection and solid tumors, but not acute infection or tumor metastases, highlighting fundamental differences with antigen-specific T cell control.
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