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Nat Commun:抗GARP:TGF-β1单抗能克服PD-1/PD-L1抑制剂耐药性

2020-09-16 xiaozeng MedSci原创

调节性T细胞(Treg)的免疫抑制作用对于外周免疫耐受的维持是不可或缺的,在癌症或慢性感染中该作用具有有害性。因此,在癌症患者中靶向Treg细胞及其功能的治疗策略的研究显得尤为重要。

调节性T细胞(Treg)的免疫抑制作用对于外周免疫耐受的维持是不可或缺的,在癌症或慢性感染中该作用具有有害性。因此,在癌症患者中靶向Treg细胞及其功能的治疗策略的研究显得尤为重要。

尽管目前使用单克隆抗体(mAb)阻断CTLA-4或PD-1抑制性途径已取得一定的进展,但绝大多数患者对T细胞介导性抗肿瘤免疫作用的原发性或获得性耐药使得患者对该免疫疗法无响应,且在大多数患者和癌症类型中发现Treg细胞似乎对抗肿瘤免疫是有害的。


TGF-β1、β2和β3能够结合一个共同的受体并在癌症中发挥着不同的作用,其可以通过促进肿瘤转移和抑制抗肿瘤免疫作用来促进肿瘤的发生发展,相反的,其还可以通过抑制恶性细胞的增殖而起到抑癌作用。既往研究显示,抑制TGF-β的整体表达水平会引起有害的促肿瘤作用。

联合阻断GARP:TGF-β1和PD-1具有抗肿瘤作用

该研究发现,表达抗GARP:TGF-β1复合物抗体的Treg能够选择性的阻断TGF-β1的产生,并抑制具有PD-1免疫治疗抗性的肿瘤的生长。而GARP:TGF-β1/PD-1阻滞剂的联合作用是FcγR功能非依赖性的免疫介导反应,其能够增加抗肿瘤CD8+T细胞的功能,而不会增加免疫细胞的浸润或清除肿瘤中的Treg细胞。研究人员还发现了表达GARP的Treg细胞,并证明转移性黑色素瘤患者的三分之一的该细胞能够产生TGF-β1。


综上研究结果显示,抗GARP:TGF-β1的单克隆抗体能够通过选择性的抑制具有促癌作用的TGF-β蛋白亚型,其可能是PD-1/PD-L1抑制剂耐药性患者的一个潜在的治疗药物。


原始出处:

de Streel, G., Bertrand, C., Chalon, N. et al. Selective inhibition of TGF-β1 produced by GARP-expressing Tregs overcomes resistance to PD-1/PD-L1 blockade in cancer. Nat Commun 11, 4545 (11 September 2020).

 

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    2021-03-07 liuli5079
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[GetPortalCommentsPageByObjectIdResponse(id=2011142, encodeId=b4f9201114287, content=<a href='/topic/show?id=0a351e34776' target=_blank style='color:#2F92EE;'>#TGF-β1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17347, encryptionId=0a351e34776, topicName=TGF-β1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sat Aug 07 15:19:14 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087769, encodeId=3f4a208e76914, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, 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topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=496f4824495, createdName=ms6980045490879608, createdTime=Fri Sep 18 13:19:14 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885942, encodeId=847c885942a1, content=<a href='/topic/show?id=e0e2803e878' target=_blank style='color:#2F92EE;'>#耐药性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=211, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80378, encryptionId=e0e2803e878, topicName=耐药性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Sep 17 02:06:08 CST 2020, time=2020-09-17, status=1, ipAttribution=)]
    2020-11-05 liye789132251
  5. [GetPortalCommentsPageByObjectIdResponse(id=2011142, encodeId=b4f9201114287, content=<a href='/topic/show?id=0a351e34776' target=_blank style='color:#2F92EE;'>#TGF-β1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17347, encryptionId=0a351e34776, topicName=TGF-β1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sat Aug 07 15:19:14 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087769, encodeId=3f4a208e76914, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, 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topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=496f4824495, createdName=ms6980045490879608, createdTime=Fri Sep 18 13:19:14 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885942, encodeId=847c885942a1, content=<a href='/topic/show?id=e0e2803e878' target=_blank style='color:#2F92EE;'>#耐药性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=211, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80378, encryptionId=e0e2803e878, topicName=耐药性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Sep 17 02:06:08 CST 2020, time=2020-09-17, status=1, ipAttribution=)]
    2021-04-04 jklm09
  6. [GetPortalCommentsPageByObjectIdResponse(id=2011142, encodeId=b4f9201114287, content=<a href='/topic/show?id=0a351e34776' target=_blank style='color:#2F92EE;'>#TGF-β1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17347, encryptionId=0a351e34776, topicName=TGF-β1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sat Aug 07 15:19:14 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087769, encodeId=3f4a208e76914, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, 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topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=496f4824495, createdName=ms6980045490879608, createdTime=Fri Sep 18 13:19:14 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885942, encodeId=847c885942a1, content=<a href='/topic/show?id=e0e2803e878' target=_blank style='color:#2F92EE;'>#耐药性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=211, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80378, encryptionId=e0e2803e878, topicName=耐药性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Sep 17 02:06:08 CST 2020, time=2020-09-17, status=1, ipAttribution=)]
    2021-05-12 changhe713
  7. [GetPortalCommentsPageByObjectIdResponse(id=2011142, encodeId=b4f9201114287, content=<a href='/topic/show?id=0a351e34776' target=_blank style='color:#2F92EE;'>#TGF-β1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=76, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17347, encryptionId=0a351e34776, topicName=TGF-β1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=f634250, createdName=chentianping, createdTime=Sat Aug 07 15:19:14 CST 2021, time=2021-08-07, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2087769, encodeId=3f4a208e76914, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=86, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, 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content=<a href='/topic/show?id=779d1389e7e' target=_blank style='color:#2F92EE;'>#PD-1/PD-L1抑制剂#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=89, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13897, encryptionId=779d1389e7e, topicName=PD-1/PD-L1抑制剂)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/WQ1WyMBGic8d2fKdCe6Cm3vaRh4X8YnlumYndC46iagNCBl9Df8RtoCaQchnFtZldHUctGJjsgsyutUlu8vPq6yQ/132, createdBy=97862500016, createdName=ms3117646317107274, createdTime=Fri Sep 18 13:19:14 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1441388, encodeId=4f0e144138868, content=<a href='/topic/show?id=58dd1e34591' target=_blank style='color:#2F92EE;'>#TGF-β#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=128, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=17345, encryptionId=58dd1e34591, topicName=TGF-β)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=496f4824495, createdName=ms6980045490879608, createdTime=Fri Sep 18 13:19:14 CST 2020, time=2020-09-18, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=885942, encodeId=847c885942a1, content=<a href='/topic/show?id=e0e2803e878' target=_blank style='color:#2F92EE;'>#耐药性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=211, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=80378, encryptionId=e0e2803e878, topicName=耐药性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=a12645, createdName=智智灵药, createdTime=Thu Sep 17 02:06:08 CST 2020, time=2020-09-17, status=1, ipAttribution=)]
    2020-09-18 smartjoy
  8. 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  9. 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  10. 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