Nature：最后一搏！死亡的肿瘤细胞释放出胞内钾离子来阻断免疫系统

2016-09-16 佚名生物谷

在一项新的研究中，来自美国国家癌症研究所和英国巴布拉汉研究所的研究人员发现当肿瘤组织死亡时从它当中泄露出来的一种无机离子起着阻止抗肿瘤免疫细胞发挥功能的作用。这一发现为开发调动免疫系统抵抗癌症的疗法提供一种新的方法。相关研究结果于2016年9月14日在线发表在Nature期刊上，论文标题为“Ionic immune suppression within the tumour microenviro

在一项新的研究中，来自美国国家癌症研究所和英国巴布拉汉研究所的研究人员发现当肿瘤组织死亡时从它当中泄露出来的一种无机离子起着阻止抗肿瘤免疫细胞发挥功能的作用。这一发现为开发调动免疫系统抵抗癌症的疗法提供一种新的方法。相关研究结果于2016年9月14日在线发表在Nature期刊上，论文标题为“Ionic immune suppression within the tumour microenvironment limits T cell effector function”。

肿瘤是由活跃增殖的细胞和死亡组织区域的混合物组成的。之前的研究已发现肿瘤能够抑制抵抗它们的免疫细胞，但是在此之前，人们并不知道这是如何实现的。这项新的研究发现肿瘤内的细胞一旦死亡就会释放钾离子到胞外空间中。钾离子是一种通常在细胞内而不是在细胞外高浓度存在的离子。胞外肿瘤环境中水平增加的钾离子降低T细胞的活性，阻止它们的抗肿瘤功能，其中T细胞是免疫系统中的一种特化的效应细胞。

研究人员对肿瘤特异性的T细胞进行分子改造以便增加它们移除来自死亡的肿瘤细胞中的钾离子。这些经过改造的T细胞能够有效地发挥着激活一种抗肿瘤免疫反应的作用，尽管它们的周围是较高水平的钾离子环境。这些T细胞经改造后表达更多的分子泵，而这些分子泵将过量的钾离子从T细胞中驱逐出去。提供这些T细胞的“钾离子输出”能力会阻止导致细胞功能障碍的高水平胞内钾离子堆积。

以这种方式修饰T细胞会增殖皮肤癌小鼠的肿瘤清除和存活率。

论文共同作者、巴布拉汉研究所淋巴细胞信号转导与发育项目团队领导Rahul Roychoudhuri博士说，“尽管已知当遭遇到外来入侵者和癌细胞时，钙离子等离子在激活T细胞中发挥着至关重要的作用，但是对胞外钾离子如何可能影响这一点，人们知之甚少。令人吃惊的是，我们发现当T细胞遭遇到肿瘤抗原时，由肿瘤中死亡的细胞释放出的高水平钾离子对钙离子具有非常少的影响，但是会阻断一种被称作PI3K通路的细胞信号通路激活。在巴布拉汉研究所，我们在涉及PI3K通路的研究中积累着大量的经验，因此我们已作出很好的准备来理解钾离子阻断T细胞激活的机制。”

这项研究揭示出肿瘤阻断T细胞抗肿瘤功能的一种新机制和鉴定出设计新的癌症免疫疗法的新靶点。论文共同通信作者、美国国家癌症研究所科学家Nicholas Restifo博士说，“这些发现对肿瘤微环境中的离子不平衡如何能够强大地阻止浸润到肿瘤中的免疫细胞的功能提供新的认识。我们特别兴奋的是，这可能有助我们开发新的疗法来激活癌症患者体内的免疫功能。”

原始出处

Robert Eil, Suman K. Vodnala, David Clever, Christopher A. Klebanoff, Madhusudhanan Sukumar, Jenny H. Pan, Douglas C. Palmer, Alena Gros, Tori N. Yamamoto, Shashank J. Patel, Geoffrey C. Guittard, Zhiya Yu, Valentina Carbonaro, Klaus Okkenhaug, David S. Schrump, W. Marston Linehan, Rahul Roychoudhuri & Nicholas P. Restifo.Ionic immune suppression within the tumour microenvironment limits T cell effector function.Nature.2016

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2016-12-30 经常头晕

#钾离子#

45 0
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2016-11-30 liye789132251

#Nat#

28 0
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2017-04-03 41514497@qq.com

#阻断#

32 0
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2016-09-20 lhl629

不错的内容，谢谢分享。

66 0
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2016-09-19 lhl629

很好的内容，谢谢分享。

66 0
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2016-09-18 hmwwww

#肿瘤细胞#

23 0
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2016-09-18 1dd8a7c5m95(暂无匿称)

学习了，赞一个！！！

69 0
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2016-09-17 yiranshixiu

肿瘤，永恒的话题

74 0
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2016-09-17 医张生

基理还是不是太清楚。

79 0
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2016-09-17 1de0a5b9m79(暂无匿称)

学习了，给了新思路，谢谢

36 0

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