Tumor-priming converts NK cells to memory-like NK cells
Tumor-priming converts NK cells to memory-like NK cells
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DOI：
10.1080/2162402x.2017.1317411
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发表时间：
2017-01-01
期刊：
影响因子：
7.2
通讯作者：
Andre, Maya C.
中科院分区：
文献类型：
--
作者：
Pal, Marina;Schwab, Lisa;Andre, Maya C.
早期的证据表明，人类自然杀伤（NK）细胞的内在能力，以获得适应性免疫功能的背景下，巨细胞病毒（CMV）感染或促炎细胞因子刺激。由于记忆NK细胞在癌症中的作用迄今为止仍然难以捉摸，并且复发性儿科急性B细胞前体白血病（BCP-ALL）患者中的过继NK细胞转移有待改善，我们提出了肿瘤引发是否可以促进记忆NK细胞的产生并增强移植物对淋巴细胞的免疫应答的问题。白血病（GvL）反应性。在这里，我们提供了大量的证据表明，幼稚的人NK细胞与小儿急性B细胞白血病或急性髓性白血病标本引发诱导功能转换为肿瘤诱导的记忆样（TIML）-NK细胞，显示出增强的肿瘤特异性细胞毒性和穿孔素合成。细胞周期分析表明，肿瘤引发可持续地改变了NK细胞活化和凋亡之间的平衡，有利于生存。此外，基因表达模式在TIML-和姜黄素诱导的记忆样（CIML）-NK细胞之间不同，其中在TIML-NK细胞中调节基因的数量明显更高。因此，肿瘤诱导的NK细胞转化触发了迄今为止未被承认的NK细胞分化阶段的出现，其可能在过继细胞转移的背景下促进GvL效应。
Fascinating earlier evidence suggests an intrinsic capacity of human natural killer (NK) cells to acquire adaptive immune features in the context of cytomegalovirus (CMV) infection or pro-inflammatory cytokine stimulation. Since the role of memory NK cells in cancer has so far remained elusive and adoptive NK cell transfer in relapsing pediatric acute B cell precursor leukemia (BCP-ALL) patients awaits improvement, we asked the question whether tumor-priming could promote the generation of memory NK cells with enhanced graft-vs.-leukemia (GvL) reactivity. Here, we provide substantial evidence that priming of naive human NK cells with pediatric acute B cell leukemia or acute myeloid leukemia specimens induces a functional conversion to tumor-induced memory-like (TIML)-NK cells displaying a heightened tumor-specific cytotoxicity and enhanced perforin synthesis. Cell cycles analyses reveal that tumor-priming sustainably alters the balance between NK cell activation and apoptosis in favor of survival. In addition, gene expression patterns differ between TIML- and cytokine-induced memory-like (CIML)-NK cells with the magnitude of regulated genes being distinctly higher in TIML-NK cells. As such, the tumor-induced conversion of NK cells triggers the emergence of a so far unacknowledged NK cell differentiation stage that might promote GvL effects in the context of adoptive cell transfer.