Sci Signal:“助推”杀手T细胞,增强实体瘤的免疫治疗效果:Science子刊

2018-04-27 M记 生物探索

细胞毒性T细胞浸润实体肿瘤的能力有限,让免疫系统的免疫监视和免疫疗法对癌症的疗效“大打折扣”。现在,来自辛辛那提大学(UC)的研究揭示了帮助CD8+ T细胞浸润某些实体肿瘤的潜在新靶点。

细胞毒性T细胞浸润实体肿瘤的能力有限,让免疫系统的免疫监视和免疫疗法对癌症的疗效“大打折扣”。现在,来自辛辛那提大学(UC)的研究揭示了帮助CD8+ T细胞浸润某些实体肿瘤的潜在新靶点。

Breast Tumor Microenvironment. Credit: Joseph Szulczewski, David Inman, Kevin Eliceiri, and Patricia Keely. NCI/ Carbone Cancer Center at the Univ. of Wisconsin

这项研究以 “A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment”为题在线发表在4月24日的《Science Signaling》杂志上。

CD8+T细胞是一种能够杀死癌细胞的T细胞。最新研究表明,瞄准kca3.1钾通道,可以恢复患者样本中CD8+ T细胞的迁移,从而有望助力T细胞进入肿瘤并消灭它们。这意味着它们可能更有效地进入肿瘤并攻击它。

“抑制钾通道的活动限制了肿瘤内的T细胞运动,” 美国加州大学医学院内科系教授Laura Conforti博士说,她是辛辛那提癌症中心和UC癌症研究所的研究员,也是该研究的通讯作者。她表示,实体肿瘤内的T细胞浸润受到肿瘤微环境中多种因素的限制,其中包括腺苷,它在实体瘤中累积并抑制肿瘤特异性T细胞。

Conforti团队分析了CD8 + T细胞在3D实验模型系统(可以复制肿瘤微环境的某些特征)中的迁移过程,发现腺苷酸存在时,它可以抑制来自癌症患者T细胞的运动,而不是来自健康捐赠者的T细胞。

她说:“患者CD8+ T细胞对腺苷的敏感性增加,与KCa3.1通道活性降低有关,但与腺苷受体的表达或信号传递无关。使用一种恢复KCa3.1通道活性的物质,可以纠正腺苷存在下患者CD8+ T细胞的迁移,这表明钾通道激活剂可能有助于增强富含腺苷的实体瘤的T细胞浸润,从而提供了另一种治疗选择。”

Conforti 表示,这一发现可能会有助于开发新的治疗药物,并结合已批准的免疫制剂治疗实体肿瘤,因为它们可以提高疗效.

原始出处:
Chimote AA, Balajthy A, Arnold MJ,et al. A defect in KCa3.1 channel activity limits the ability of CD8+ T cells from cancer patients to infiltrate an adenosine-rich microenvironment.Sci Signal. 2018 Apr 24;11(527). pii: eaaq1616. doi: 10.1126/scisignal.aaq1616.

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    2018-07-24 yaanren
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    2018-07-15 1e145228m78(暂无匿称)

    学习了.谢谢作者分享!

    0

  4. 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encryptionId=ae7816304dc, topicName=Sign)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e9ed371, createdName=楚秀娟, createdTime=Sat Sep 01 16:48:00 CST 2018, time=2018-09-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1375809, encodeId=b48713e5809cb, content=<a href='/topic/show?id=2949159989d' target=_blank style='color:#2F92EE;'>#SCIE#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=36, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=15998, encryptionId=2949159989d, topicName=SCIE)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=17a3387, createdName=jichang, createdTime=Sun Apr 29 01:48:00 CST 2018, time=2018-04-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1031739, encodeId=46081031e39f1, content=谢谢梅斯提供这么好的信息,学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=43, replyNumber=0, topicName=null, topicId=null, 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createdAvatar=, createdBy=4fa72112970, createdName=1821f909bem, createdTime=Fri Apr 27 13:05:50 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309799, encodeId=229f309e995f, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Fri Apr 27 12:31:05 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309790, encodeId=7379309e9058, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Fri Apr 27 12:24:22 CST 2018, time=2018-04-27, status=1, ipAttribution=)]
    2018-09-01 楚秀娟
  5. 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createdAvatar=, createdBy=4fa72112970, createdName=1821f909bem, createdTime=Fri Apr 27 13:05:50 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309799, encodeId=229f309e995f, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Fri Apr 27 12:31:05 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309790, encodeId=7379309e9058, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Fri Apr 27 12:24:22 CST 2018, time=2018-04-27, status=1, ipAttribution=)]
    2018-04-29 jichang
  6. 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createdAvatar=, createdBy=4fa72112970, createdName=1821f909bem, createdTime=Fri Apr 27 13:05:50 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309799, encodeId=229f309e995f, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Fri Apr 27 12:31:05 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309790, encodeId=7379309e9058, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Fri Apr 27 12:24:22 CST 2018, time=2018-04-27, status=1, ipAttribution=)]
    2018-04-27 内科新手

    谢谢梅斯提供这么好的信息,学到很多

    0

  7. 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createdAvatar=, createdBy=4fa72112970, createdName=1821f909bem, createdTime=Fri Apr 27 13:05:50 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309799, encodeId=229f309e995f, content=阅, beContent=null, objectType=article, channel=null, level=null, likeNumber=50, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/vi_32/fhZdOu27e88Voqh19n8eF8cLplo8L4nicKtH0WnE3KFELXns5XDu8rsiceK2HHDZc2SEStia5VV3Pia2QLMVqlWbHw/0, createdBy=6e012139475, createdName=神功盖世, createdTime=Fri Apr 27 12:31:05 CST 2018, time=2018-04-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=309790, encodeId=7379309e9058, content=学习了新知识, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Fri Apr 27 12:24:22 CST 2018, time=2018-04-27, status=1, ipAttribution=)]
    2018-04-27 131****1460

    学习了受益匪浅

    0

  8. 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createdAvatar=https://img.medsci.cn/20201006/4db877c2887649beb09cb5effd0b38c7/916f66edd48a4e77b20ebc3e14b6e45c.jpg, createdBy=141e1980133, createdName=Y—xianghai, createdTime=Fri Apr 27 12:24:22 CST 2018, time=2018-04-27, status=1, ipAttribution=)]
    2018-04-27 1821f909bem

    钾离子通道!

    0

  9. 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    2018-04-27 神功盖世

    0

  10. 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    2018-04-27 Y—xianghai

    学习了新知识

    0

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