Cancer Immunol Res:COX-2抑制剂对抗癌治疗有帮助?

2017-07-21 枫丹白露 来宝网

在临床前研究中,构成表达蛋白质吲哚胺2,3-双加氧酶(IDO1)的肿瘤对环氧合酶-2(COX-2)抑制剂塞来昔布(Celebrex)有反应,并且改善了某些T细胞亚群的浸润,使其更有可能以应对抗PD1疗法。

临床前研究中,构成表达蛋白质吲哚胺2,3-双加氧酶(IDO1)的肿瘤对环氧合酶-2(COX-2)抑制剂塞来昔布(Celebrex)有反应,并且改善了某些T细胞亚群的浸润,使其更有可能以应对抗PD1疗法。

该研究发表在美国癌症研究协会癌症免疫研究杂志上。

“癌症免疫治疗中的一个关键挑战是了解为什么有些患者应对免疫治疗,但是其他许多患者没有反应,”Van den Eynde说。 “如果我们明白为什么,我们可以选择和治疗只有那些可以从治疗中受益的患者,但最重要的是,我们可以制定策略,使免疫疗法在目前没有反应的人中起作用。”

Van den Eynde解释说,许多肿瘤使用IDO1来保护自己免受免疫攻击。其中有些人在被T细胞攻击时开始建立和提高保护,这被称为适应性抵抗。在这样的肿瘤中,IDO1表达与炎症和T细胞浸润有关。

然而,一些肿瘤组成型(连续)产生IDO1,并且在任何免疫攻击之前使它们的屏蔽作用准备和升高。这样的肿瘤被完全保护,并可以立即禁用T细胞来防止T细胞的侵袭。 Van den Eynde说:“这就是我们所说的固有抗性,可能解释为什么一些肿瘤是不被T细胞浸润的。

他补充道:“我们想了解使得一些肿瘤组成型表达IDO1的分子机制。

Van den Eynde及其同事使用两种人黑素瘤细胞系,首先证明COX-2及其产物前列腺素E2(PGE2)通过利用MAPK,PKC和PI3K细胞信号通路引起IDO1的组成型表达。这些结果也适用于其他人类肿瘤细胞系,包括肺,卵巢和头颈癌细胞系。 Van den Eynde指出:“这些数据证明COX-2通过组织型表达IDO1来驱动肿瘤诱导的免疫抑制。”

接下来,他们表明用人类淋巴细胞重建的携带具有组成型IDO1表达的人类卵巢肿瘤异种移植物的免疫缺陷小鼠对塞来昔布以及IDO1抑制剂,即表面活性剂作出反应。 “我们用COX-2抑制剂和IDO1抑制剂观察到的结果是相同的,这是一个惊喜,”Van den Eynde说。使两种化合物以两种不同的作用方式作用于同一途径总是非常有用的:如果肿瘤开始抵抗一种化合物,它们可能仍然对另一种化合物敏感。

研究人员从Broad Institute开发了1,041种不同人类肿瘤细胞系的转录组学数据,发现IDO1表达与COX-2 / PGE2轴在几种癌症类型(包括胃,胰腺,肝和肺癌)中的活化之间存在相关性。

Van den Eynde说:“我们的研究提供了一个明确的理由,在诊所中测试抗PD1免疫治疗和COX-2抑制剂的组合。 “这应该是直接的,因为抗PD1和COX-2抑制剂已被批准用于不同情况下的临床应用。”该组的初步分析显示,大约10%至50%的人类肿瘤组成型表达IDO1,这取决于肿瘤类型。

原始出处:

Marc Hennequart, Luc Pilotte, et al. Constitutive IDO1 Expression in Human Tumors Is Driven by Cyclooxygenase-2 and Mediates Intrinsic Immune Resistance. Cancer Immunology Research Published OnlineFirst July 21, 2017  doi: 10.1158/2326-6066.CIR-16-0400

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    2017-07-23 ylzr123

    好文,值得点赞!认真学习,应用于实践!谢谢分享给广大同好!

    0

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    2017-07-23 luominglian113

    学习了,谢谢分享

    0

  7. [GetPortalCommentsPageByObjectIdResponse(id=1934500, encodeId=ffbe1934500d2, content=<a href='/topic/show?id=27c85552e65' target=_blank style='color:#2F92EE;'>#抗癌治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55527, encryptionId=27c85552e65, topicName=抗癌治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9df476, createdName=fyxzlh, createdTime=Sat May 26 05:03:00 CST 2018, time=2018-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703410, encodeId=3fbf1e034105a, content=<a href='/topic/show?id=9b4751449d' target=_blank style='color:#2F92EE;'>#COX-2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5144, encryptionId=9b4751449d, topicName=COX-2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=387330501690, createdName=chenlianhui, createdTime=Mon Oct 02 22:03:00 CST 2017, time=2017-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995493, encodeId=15551995493f2, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Sat Mar 03 17:03:00 CST 2018, time=2018-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533674, encodeId=07d015336e479, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Sun Jul 23 11:03:00 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225358, encodeId=7c542253587c, content=好文,值得点赞!认真学习,应用于实践!谢谢分享给广大同好!, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun Jul 23 09:34:35 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225224, encodeId=a0252252247e, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Sun Jul 23 00:36:27 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851493, encodeId=e103185149374, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Sep 20 06:03:00 CST 2017, time=2017-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225013, encodeId=6401225013a9, content=阿司匹林用处大, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/777425ccaec245867e499b9754164208.jpg, createdBy=74ec2091836, createdName=1301f486dcm, createdTime=Sat Jul 22 09:36:02 CST 2017, time=2017-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224872, encodeId=5a792248e20d, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sat Jul 22 06:25:07 CST 2017, time=2017-07-22, status=1, ipAttribution=)]
    2017-09-20 jklm09
  8. [GetPortalCommentsPageByObjectIdResponse(id=1934500, encodeId=ffbe1934500d2, content=<a href='/topic/show?id=27c85552e65' target=_blank style='color:#2F92EE;'>#抗癌治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55527, encryptionId=27c85552e65, topicName=抗癌治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9df476, createdName=fyxzlh, createdTime=Sat May 26 05:03:00 CST 2018, time=2018-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703410, encodeId=3fbf1e034105a, content=<a href='/topic/show?id=9b4751449d' target=_blank style='color:#2F92EE;'>#COX-2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5144, encryptionId=9b4751449d, topicName=COX-2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=387330501690, createdName=chenlianhui, createdTime=Mon Oct 02 22:03:00 CST 2017, time=2017-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995493, encodeId=15551995493f2, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Sat Mar 03 17:03:00 CST 2018, time=2018-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533674, encodeId=07d015336e479, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Sun Jul 23 11:03:00 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225358, encodeId=7c542253587c, content=好文,值得点赞!认真学习,应用于实践!谢谢分享给广大同好!, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun Jul 23 09:34:35 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225224, encodeId=a0252252247e, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Sun Jul 23 00:36:27 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851493, encodeId=e103185149374, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Sep 20 06:03:00 CST 2017, time=2017-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225013, encodeId=6401225013a9, content=阿司匹林用处大, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/777425ccaec245867e499b9754164208.jpg, createdBy=74ec2091836, createdName=1301f486dcm, createdTime=Sat Jul 22 09:36:02 CST 2017, time=2017-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224872, encodeId=5a792248e20d, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sat Jul 22 06:25:07 CST 2017, time=2017-07-22, status=1, ipAttribution=)]
    2017-07-22 1301f486dcm

    阿司匹林用处大

    0

  9. [GetPortalCommentsPageByObjectIdResponse(id=1934500, encodeId=ffbe1934500d2, content=<a href='/topic/show?id=27c85552e65' target=_blank style='color:#2F92EE;'>#抗癌治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=55527, encryptionId=27c85552e65, topicName=抗癌治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=c9df476, createdName=fyxzlh, createdTime=Sat May 26 05:03:00 CST 2018, time=2018-05-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1703410, encodeId=3fbf1e034105a, content=<a href='/topic/show?id=9b4751449d' target=_blank style='color:#2F92EE;'>#COX-2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=38, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5144, encryptionId=9b4751449d, topicName=COX-2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=387330501690, createdName=chenlianhui, createdTime=Mon Oct 02 22:03:00 CST 2017, time=2017-10-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1995493, encodeId=15551995493f2, content=<a href='/topic/show?id=992411149e' target=_blank style='color:#2F92EE;'>#2抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=31, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=1114, encryptionId=992411149e, topicName=2抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=55683, createdName=仁医06, createdTime=Sat Mar 03 17:03:00 CST 2018, time=2018-03-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1533674, encodeId=07d015336e479, content=<a href='/topic/show?id=34e6514391' target=_blank style='color:#2F92EE;'>#COX-2#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5143, encryptionId=34e6514391, topicName=COX-2)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=544412475251, createdName=手留余香, createdTime=Sun Jul 23 11:03:00 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225358, encodeId=7c542253587c, content=好文,值得点赞!认真学习,应用于实践!谢谢分享给广大同好!, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/NUyjXTCJjo7s7ZCKOmmbBTD6nE7gcd5OZpvyGEzkxBP3S275k5ZJVrsPkotZhBglRHM9rKvcj1OgkssqhcnoPw8zIaMZTF8c/0, createdBy=4c441942088, createdName=ylzr123, createdTime=Sun Jul 23 09:34:35 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225224, encodeId=a0252252247e, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=44, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=550d2008262, createdName=luominglian113, createdTime=Sun Jul 23 00:36:27 CST 2017, time=2017-07-23, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1851493, encodeId=e103185149374, content=<a href='/topic/show?id=f0a254918f0' target=_blank style='color:#2F92EE;'>#抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=21, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=54918, encryptionId=f0a254918f0, topicName=抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=44a360, createdName=jklm09, createdTime=Wed Sep 20 06:03:00 CST 2017, time=2017-09-20, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=225013, encodeId=6401225013a9, content=阿司匹林用处大, beContent=null, objectType=article, channel=null, level=null, likeNumber=54, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/07/17/777425ccaec245867e499b9754164208.jpg, createdBy=74ec2091836, createdName=1301f486dcm, createdTime=Sat Jul 22 09:36:02 CST 2017, time=2017-07-22, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=224872, encodeId=5a792248e20d, content=学习了谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=00501987275, createdName=130****4638, createdTime=Sat Jul 22 06:25:07 CST 2017, time=2017-07-22, status=1, ipAttribution=)]
    2017-07-22 130****4638

    学习了谢谢分享

    0

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