Blood:尼洛替尼联合PD-L1阻滞可逆转CD4+T细胞耗竭预防B-ALL复发

2022-08-19 MedSci原创 MedSci原创

酪氨酸激酶抑制剂尼洛替尼联合PD-L1阻滞可逆转CD4+T细胞耗竭,进而预防B 细胞急性淋巴细胞白血病的复发

得益于嵌合抗原受体 (CAR) T 细胞和双特异性 T 细胞接合器的出现,急性淋巴细胞白血病患者的预后得到了显著改善;尽管取得了这些进展,但仍有一部分患者会复发。T 细胞衰竭最近被认为是这些患者复发的重要驱动因素。

事实上,CD4+ T 细胞表型衰竭可以预测 B 细胞急性淋巴细胞白血病 (B-ALL) 的复发和较差的总生存率。因此,对抗 T 细胞衰竭的疗法,如免疫检查点封闭,可改善白血病免疫监测和预防复发。

在该研究中,研究人员利用 Ph+ B-ALL小鼠模型和人骨髓活检样本来评估 CD4+ T细胞耗竭的基本性质,以及联合抗 PD-L1 为基础的检查点封闭和靶向 BCR-ABL 癌蛋白的酪氨酸激酶抑制剂的临床前治疗潜力。


不同分组小鼠的生存预后

单细胞 RNA 测序分析显示,B-ALL 诱导出了 CD4+ T细胞的一个独特亚群,同时具有细胞毒性和辅助功能。酪氨酸激酶抑制剂尼洛替尼和抗 PD-L1 的联合治疗显著改善了白血病小鼠的长期生存情况

在治疗前清除CD4+ T细胞会完全消掉生存益处,这提示 CD4+ T细胞是保护性抗白血病免疫反应的关键驱动因素。此外,使用抗 PD-L1 治疗会导致具有上述辅助/细胞毒性表型的白血病特异性CD4+ T 细胞出现克隆扩增,以及衰竭标志物的表达减少。

综上,该研究结果支持在临床试验中使用PD1/PD-L1检查点阻滞剂的尝试,并强调了CD4+ T细胞功能障碍在限制内源性抗白血病反应中的重要性。

 

原始出处:

Tracy Sean I,Venkatesh Hrishi,Hekim Can et al. Combining nilotinib and PD-L1 blockade reverses CD4+ T-cell dysfunction and prevents relapse in acute B-cell leukemia.[J] .Blood, 2022, 140: 335-348. https://doi.org/10.1182/blood.2021015341

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    2022-12-11 qidongfanjian
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  4. [GetPortalCommentsPageByObjectIdResponse(id=1984726, encodeId=60d81984e26ac, content=<a href='/topic/show?id=7c854e3738a' target=_blank style='color:#2F92EE;'>#尼洛替尼#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=47373, encryptionId=7c854e3738a, topicName=尼洛替尼)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=ca282500032, createdName=1249857fm32暂无昵称, createdTime=Tue Mar 28 00:46:31 CST 2023, time=2023-03-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1864310, encodeId=eb64186431044, content=<a href='/topic/show?id=f930432538' target=_blank style='color:#2F92EE;'>#CD4#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4325, encryptionId=f930432538, topicName=CD4)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b09892, createdName=qidongfanjian, createdTime=Sun Dec 11 19:46:31 CST 2022, time=2022-12-11, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2029473, encodeId=f67d20294e3c0, content=<a href='/topic/show?id=21a71803689' target=_blank style='color:#2F92EE;'>#T细胞耗竭#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=68, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=18036, encryptionId=21a71803689, topicName=T细胞耗竭)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=99cf2500102, createdName=zjshifan_98647306, createdTime=Wed Aug 31 22:46:31 CST 2022, time=2022-08-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1652611, encodeId=07a61652611e5, content=<a href='/topic/show?id=5082432634' target=_blank style='color:#2F92EE;'>#CD4+#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=39, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4326, encryptionId=5082432634, topicName=CD4+)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4c1624305102, createdName=xuyu, createdTime=Wed May 10 19:46:31 CST 2023, time=2023-05-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1255170, encodeId=3b6d12551e090, content=<a href='/topic/show?id=be71139214f' target=_blank style='color:#2F92EE;'>#PD-L1#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=70, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13921, encryptionId=be71139214f, topicName=PD-L1)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=e76f39, createdName=smartjoy, createdTime=Sun Aug 21 06:46:31 CST 2022, time=2022-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1329640, encodeId=12081329640df, content=<a href='/topic/show?id=bb96232801' target=_blank style='color:#2F92EE;'>#ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=55, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=2328, encryptionId=bb96232801, topicName=ALL)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdqq.qlogo.cn/qqapp/1103841572/C2EFD5CFB07FE291138AD4FD0C98E3DE/100, createdBy=e3d52500031, createdName=膀胱癌, createdTime=Sun Aug 21 06:46:31 CST 2022, time=2022-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1423267, encodeId=2412142326e86, content=<a href='/topic/show?id=18f43131be' target=_blank style='color:#2F92EE;'>#B-ALL#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=45, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=3131, encryptionId=18f43131be, topicName=B-ALL)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=7c123763345, createdName=chenzhuanggui, createdTime=Sun Aug 21 06:46:31 CST 2022, time=2022-08-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1500977, encodeId=8db515009e72c, content=<a href='/topic/show?id=04794329fc' target=_blank style='color:#2F92EE;'>#CD4+T细胞#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4329, encryptionId=04794329fc, topicName=CD4+T细胞)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cd149483945, createdName=海豹, createdTime=Sun Aug 21 06:46:31 CST 2022, time=2022-08-21, status=1, ipAttribution=)]
    2023-05-10 xuyu
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    2022-08-21 smartjoy
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    2022-08-21 膀胱癌
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