PNAS:抑制这2个蛋白,可强化T细胞抗肿瘤和抗感染

2018-08-22 风铃 生物探索

T细胞是我们体内的“带刀侍卫”,它是机体免疫系统的重要组成部分之一。但在癌症或慢性感染(如HIV感染)中,T细胞往往会大量死亡或停止正常的工作,使我们难以抵抗疾病。不过,加州大学旧金山分校(UCSF)的科学家们最近发现了两个蛋白靶点,抑制它们的活性可以避免这种情况的出现。

忠心耿耿的侍卫:CD8 T细胞

当人体遭到病原体入侵时,CD8 T细胞会迅速繁殖,成为“效应细胞”。它们是保护我们的侍卫,会主动出击杀死受感染的细胞。但一旦病原体消失,这些具有攻击性的效应细胞就死亡,以确保它们不会攻击正常的细胞。

然而仍然有一小部分效应细胞会存活下来,成为记忆细胞,它们更像是专职守卫,静静守在你的身体里。当遇到相同的病原体入侵者时,这些记忆细胞就会更快地做出反应,迅速消灭这种病原体。

不过,T细胞的这种保护也并非坚不可摧,在面对肿瘤或类似HIV的慢性感染时,这些忠心耿耿的侍卫往往有心无力。

强化效应T细胞

8月20日,加州大学旧金山分校的Shomyseh Sanjabi博士和她的团队在《PNAS》杂志上发表了最新的研究成果,在这篇题为“Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells”的论文中,他们报道了发现的两个靶点分子:Sprouty 1和Sprouty 2,它们与效应T细胞的存活状况以及记忆CD8 T细胞的发育有关,这在癌症和慢性感染的免疫治疗方面有着巨大的潜力。



该团队使用了Sanjabi博士过去10年来一直在开发的动物模型,发现当从CD8 T细胞中删除了Sprouty 1和Sprouty 2后,更多的效应细胞得以存活并转变为了记忆细胞。同时,他们还证明,缺乏Sprouty的记忆细胞比正常的记忆细胞具有更好的抗病原体能力。

有趣的是,这些记忆细胞比正常的CD8 T细胞消耗的葡萄糖少,虽然效应细胞依赖于葡萄糖来生存,但记忆细胞通常消耗更多的脂肪酸。

“肿瘤细胞会消耗大量葡萄糖,因此效应细胞难以在肿瘤环境中存活,因为它没有足够的能量来源。”这篇论文的第一作者Hesham Shehata博士解释说,“虽然记忆细胞通常不依赖于葡萄糖,但我们的研究表明,没有Sprouty 1和Sprouty 2的效应细胞消耗更少的葡萄糖,因此它们可以很好地存活于肿瘤环境中发挥作用。”


Shomyseh Sanjabi博士(右)和Hesham Shehata博士(左)

改进免疫疗法:抗肿瘤抗感染双管齐下

Sanjabi博士的这项研究提供了一种全新的方法来增加记忆CD8 T细胞的数量,这可以为改进抗肿瘤和抗感染的免疫疗法提供帮助。

“通过揭示Sprouty 1和Sprouty 2的作用,我们的工作发现了T细胞的潜力。”Shehata博士说,“缺少Sprouty 1和Sprouty 2的细胞不仅具有巨大的抗肿瘤潜力,还具有抗慢性病毒感染的潜力。”

例如,潜伏了HIV病毒的活化细胞是艾滋病治疗的主要障碍,但删除两个Sprouty分子后,记忆细胞可能会更好地存活,这将有利于免疫系统识别、杀灭这些携带潜伏病毒的细胞。

对于肿瘤免疫疗法来说,最近的研究表明,使用效应细胞治疗的患者往往会复发,而使用记忆细胞治疗则可以帮助减少肿瘤大小甚至完全消除肿瘤。

“科学界同行们对这种既能增加记忆CD8 T细胞数目,又能改善其发育状况和功能的方法非常感兴趣,因为在免疫疗法中,使用记忆细胞的效果要比使用效应T细胞好。”Sanjabi博士解释道,“我们的研究可以与CAR T细胞对抗肿瘤的研究相结合,也可以与像CRISPR这样的基因组编辑技术结合使用,使它们更有效。” 

原始出处:

Hesham M. Shehata, Shahzada Khan, Elise Chen, et.al. Lack of Sprouty 1 and 2 enhances survival of effector CD8+ T cells and yields more protective memory cells. PNAS August 20, 2018. 201808320; published ahead of print August 20, 2018.

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    2019-03-06 drwjr
  2. [GetPortalCommentsPageByObjectIdResponse(id=1856204, encodeId=097f1856204a4, content=<a href='/topic/show?id=f32014428fc' target=_blank style='color:#2F92EE;'>#PNAS#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=14428, encryptionId=f32014428fc, topicName=PNAS)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=08e964, createdName=drwjr, createdTime=Wed Mar 06 05:35:00 CST 2019, time=2019-03-06, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=341171, encodeId=035a3411e149, content=哈哈哈,学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e1ee1608797, createdName=huangshang9812, createdTime=Mon Aug 27 14:26:41 CST 2018, time=2018-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340284, encodeId=4674340284c9, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTLbTp9nZtjwVrSZNxAXbAicnKQWnic2eBdJUQYhxO36XdkstSicr7FVF8p5ReH4omtmsbnLdvZLiaJJ1A/132, createdBy=8bff2327056, createdName=kafei, createdTime=Thu Aug 23 07:13:34 CST 2018, time=2018-08-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340191, encodeId=ece634019139, content=学习了, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://login.medsci.cn/upload/avatar/f3d88083d8829740786bed95c22464d1/e325f3af93bb747a620d16c209094d69.jpg, createdBy=9efb2014947, createdName=小小小麦兜, createdTime=Wed Aug 22 19:51:00 CST 2018, time=2018-08-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=340166, encodeId=ad1e34016629, content=谢谢分享学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4o2XVpJ6449yqDsjibydI5HnJ8MibGxNn4HZiaZib0bdfibbwoz3KQrIyN9AGxq36ZlZRNicYlPfOOWMtwgsajY6mGNFiaPclFdowjD0/0, createdBy=97bd1338592, createdName=清风拂面, createdTime=Wed Aug 22 15:10:21 CST 2018, time=2018-08-22, status=1, ipAttribution=)]
    2018-08-27 huangshang9812

    哈哈哈,学习了

    0

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    2018-08-23 kafei

    学习了谢谢分享

    0

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    2018-08-22 小小小麦兜

    学习了

    0

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    2018-08-22 清风拂面

    谢谢分享学习

    0

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饮食诱发的糖尿病,肥胖和心脏病是全球死亡的主要原因。在为这些相关慢性疾病寻找新的治疗方法时,耶鲁的研究人员调查了一种名为ANGPTL4的蛋白质。蛋白质在调节脂蛋白代谢过程中起着重要作用,脂蛋白能够转运血液中的脂肪和脂质,并且与人类心脏疾病风险增加有关。

Cell Death Disease:细胞癌变与“自毁蛋白”无处立足有关

俄罗斯科研人员近日新发现了一种细胞癌变的背后机制:正常情况下,细胞的程序性死亡机制会令有癌变迹象的细胞死亡,但若引发癌细胞自毁的信号分子蛋白在细胞膜表面找不到立足之地,就无法抑制癌变进程。

Cell:美科学家发现感受血压的蛋白质有望用来治疗中风

美国科学家发现一种可“感受”血压并“告知”小动脉何时扩张的蛋白质,有望通过激活这种蛋白质来治疗缺血性中风。