Blood:JAK/STAT抑制可增强CD8 T细胞对地塞米松诱导性细胞凋亡的敏感性

2020-08-10 MedSci原创 MedSci原创

细胞因子风暴综合征(CSS)是一种严重的超炎症状态,其特征是免疫系统过度激活,导致器官损伤和患者死亡。噬血细胞淋巴组织细胞增多症(HLH)是一种典型的CSS,其五年生存率仅为60%。

细胞因子风暴综合征(CSS)是一种严重的超炎症状态,其特征是免疫系统过度激活,导致器官损伤和患者死亡。噬血细胞淋巴组织细胞增多症(HLH)是一种典型的CSS,其五年生存率仅为60%,是一种常伴有细胞介导的细胞毒性遗传缺陷的疾病。HLH的一线治疗药物包括糖皮质激素地塞米松(DEX)和化疗药物依托泊苷(etoposide)。

但很多患者对这种治疗不耐受,或者在初始治疗缓解后会发生复发。值得注意的是,在HLH中,多种细胞因子升高,激活了JAK/STAT通路;JAK1/2抑制剂鲁索替尼(RUX)已在小鼠HLH模型和难治性疾病人类患者中显示出疗效。

近期,研究人员发现,细胞因子诱导的JAK/STAT信号介导了T细胞急性淋巴细胞白血病(T-ALL)细胞对地塞米松的抵抗,RUX可以有效地逆转这种耐药性。基于这些发现,Meyer等人假设细胞因子介导的JAK/STAT信号可能也会促进HLH的地塞米松耐药,RUX治疗或也可克服这一现象。

通过体外实验,在HLH小鼠模型和原发患者样本中,Meyer等人证明了HLH的高细胞激酶血症降低了CD8 T细胞的凋亡潜能,导致了地塞米松的相对抵抗。暴露于RUX后,这种凋亡潜能被恢复,从而在体外增强CD8 T细胞对地塞米松诱导的凋亡的敏感性,并显著减少体内组织免疫病理学和HLH病的表现。

综上所述,本研究结果为联合使用DEX和RUX以增强DEX的淋巴毒性效应改善HLH和相关CSS患者的预后提供了理论依据。

原始出处:

Lauren Meyer,et al. JAK/STAT pathway inhibition sensitizes CD8 T cells to dexamethasone-induced apoptosis in hyperinflammation. Blood. June 12,2020.

版权声明:
本网站所有内容来源注明为“梅斯医学”或“MedSci原创”的文字、图片和音视频资料,版权均属于梅斯医学所有。非经授权,任何媒体、网站或个人不得转载,授权转载时须注明来源为“梅斯医学”。其它来源的文章系转载文章,或“梅斯号”自媒体发布的文章,仅系出于传递更多信息之目的,本站仅负责审核内容合规,其内容不代表本站立场,本站不负责内容的准确性和版权。如果存在侵权、或不希望被转载的媒体或个人可与我们联系,我们将立即进行删除处理。
在此留言
评论区 (5)
#插入话题
  1. [GetPortalCommentsPageByObjectIdResponse(id=1738046, encodeId=59661e380467f, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Fri May 28 13:52:41 CST 2021, time=2021-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813282, encodeId=9b1018132821e, content=<a href='/topic/show?id=92b5918e845' target=_blank style='color:#2F92EE;'>#诱导性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91878, encryptionId=92b5918e845, topicName=诱导性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Mar 24 04:52:41 CST 2021, time=2021-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340318, encodeId=cca813403186a, content=<a href='/topic/show?id=bd5ce780493' target=_blank style='color:#2F92EE;'>#细胞凋亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77804, encryptionId=bd5ce780493, topicName=细胞凋亡)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/EFCEF19303EB52B3F41B30C45995AF2C/100, createdBy=8e712500159, createdName=ms8538335253054589, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1388521, encodeId=6aaf13885218e, content=<a href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605405, encodeId=0988160540595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=)]
  2. [GetPortalCommentsPageByObjectIdResponse(id=1738046, encodeId=59661e380467f, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Fri May 28 13:52:41 CST 2021, time=2021-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813282, encodeId=9b1018132821e, content=<a href='/topic/show?id=92b5918e845' target=_blank style='color:#2F92EE;'>#诱导性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91878, encryptionId=92b5918e845, topicName=诱导性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Mar 24 04:52:41 CST 2021, time=2021-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340318, encodeId=cca813403186a, content=<a href='/topic/show?id=bd5ce780493' target=_blank style='color:#2F92EE;'>#细胞凋亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77804, encryptionId=bd5ce780493, topicName=细胞凋亡)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/EFCEF19303EB52B3F41B30C45995AF2C/100, createdBy=8e712500159, createdName=ms8538335253054589, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1388521, encodeId=6aaf13885218e, content=<a href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605405, encodeId=0988160540595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=)]
    2021-03-24 wgx306
  3. [GetPortalCommentsPageByObjectIdResponse(id=1738046, encodeId=59661e380467f, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Fri May 28 13:52:41 CST 2021, time=2021-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813282, encodeId=9b1018132821e, content=<a href='/topic/show?id=92b5918e845' target=_blank style='color:#2F92EE;'>#诱导性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91878, encryptionId=92b5918e845, topicName=诱导性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Mar 24 04:52:41 CST 2021, time=2021-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340318, encodeId=cca813403186a, content=<a href='/topic/show?id=bd5ce780493' target=_blank style='color:#2F92EE;'>#细胞凋亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77804, encryptionId=bd5ce780493, topicName=细胞凋亡)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/EFCEF19303EB52B3F41B30C45995AF2C/100, createdBy=8e712500159, createdName=ms8538335253054589, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1388521, encodeId=6aaf13885218e, content=<a href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605405, encodeId=0988160540595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=)]
  4. [GetPortalCommentsPageByObjectIdResponse(id=1738046, encodeId=59661e380467f, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Fri May 28 13:52:41 CST 2021, time=2021-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813282, encodeId=9b1018132821e, content=<a href='/topic/show?id=92b5918e845' target=_blank style='color:#2F92EE;'>#诱导性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91878, encryptionId=92b5918e845, topicName=诱导性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Mar 24 04:52:41 CST 2021, time=2021-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340318, encodeId=cca813403186a, content=<a href='/topic/show?id=bd5ce780493' target=_blank style='color:#2F92EE;'>#细胞凋亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77804, encryptionId=bd5ce780493, topicName=细胞凋亡)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/EFCEF19303EB52B3F41B30C45995AF2C/100, createdBy=8e712500159, createdName=ms8538335253054589, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1388521, encodeId=6aaf13885218e, content=<a href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605405, encodeId=0988160540595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=)]
  5. [GetPortalCommentsPageByObjectIdResponse(id=1738046, encodeId=59661e380467f, content=<a href='/topic/show?id=0abd10215e0' target=_blank style='color:#2F92EE;'>#JAK#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=24, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10215, encryptionId=0abd10215e0, topicName=JAK)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=6e8634348903, createdName=肉我只吃一口, createdTime=Fri May 28 13:52:41 CST 2021, time=2021-05-28, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1813282, encodeId=9b1018132821e, content=<a href='/topic/show?id=92b5918e845' target=_blank style='color:#2F92EE;'>#诱导性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=30, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=91878, encryptionId=92b5918e845, topicName=诱导性)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4193478, createdName=wgx306, createdTime=Wed Mar 24 04:52:41 CST 2021, time=2021-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1340318, encodeId=cca813403186a, content=<a href='/topic/show?id=bd5ce780493' target=_blank style='color:#2F92EE;'>#细胞凋亡#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=77804, encryptionId=bd5ce780493, topicName=细胞凋亡)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdqq.qlogo.cn/qqapp/1103841572/EFCEF19303EB52B3F41B30C45995AF2C/100, createdBy=8e712500159, createdName=ms8538335253054589, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1388521, encodeId=6aaf13885218e, content=<a href='/topic/show?id=7ef25e5346b' target=_blank style='color:#2F92EE;'>#敏感性#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=32, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=57534, encryptionId=7ef25e5346b, topicName=敏感性)], attachment=null, authenticateStatus=null, createdAvatar=https://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTJnkE6UvGFfMS41qV0RicWvVTTeLMicqibeZH5GqO4YhNicyl1Y9jFhylIUBn9ntPYy9jhk5hrfic5cRYw/132, createdBy=5f822500020, createdName=ms5236388012055669, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1605405, encodeId=0988160540595, content=<a href='/topic/show?id=94c9436340' target=_blank style='color:#2F92EE;'>#CD8#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=4363, encryptionId=94c9436340, topicName=CD8)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=4bac19388006, createdName=ms691033630344116, createdTime=Wed Aug 12 06:52:41 CST 2020, time=2020-08-12, status=1, ipAttribution=)]

相关资讯

Blood:鲁索替替尼与噬血细胞综合征

噬红细胞性淋巴细胞与组织细胞增多症(HLH,又称噬血细胞综合征)是一种致死性疾病,特征是T细胞和巨噬细胞过度激活,产生过量的促炎细胞因子,包括干扰素-γ(IFNγ)。Sabrin Albeituni等人既往发现Janus激酶(JAK)抑制剂鲁索替尼可抑制T细胞活化,减轻HLH模型(用淋巴细胞脉络丛脑膜炎病毒[LCMV]感染穿孔素缺陷[Prf1-/-]小鼠)的炎症反应。鲁索替尼抑制IFNγ的下游信号

Blood:Epo刺激T细胞可增强过继性T细胞疗法的抗肿瘤活性

在癌症的过继性T细胞免疫疗法中,效应细胞的扩增和持续存在是反应的关键决定因素。目前,尚不明确T淋巴细胞是否可通过其异位表达的野生型受体或可增强红细胞前体Epo信号的截断体(EpoRm)对促红细胞生成素(Epo)敏感,Vinanica等人对此进行研究。

FDA授予Jakavi(鲁索替尼)治疗急性移植物抗宿主病(GVHD)的突破性药物资格

Incyte制药公司近日宣布,美国食品和药物管理局(FDA)已授予Jakavi(ruxolitinib,鲁索替尼)治疗急性移植物抗宿主病(graft-versus-host disease,GVHD)的突破性药物资格(BTD)。移植物抗宿主病(GVHD)是由于移植物的抗宿主反应而引起的一种免疫性疾病,是异基因造血干细胞移植的主要并发症和造成死亡的主要原因。GVHD患者最常见的受累器官为皮肤、胃

J Clin Oncol:鲁索替尼治疗有无CSF3R突变的CNL或aCML患者的疗效和安全性

集落刺激因子-3受体(CSF3R)-T618I是慢性中性粒细胞白血病(CNL)和非典型性慢性髓系白血病(aCML)的一种复发性激活突变,导致JAK-STAT信号通路组成性激活。现研究人员尝试在不考虑CSF3R突变状态的情况下评估JAK1/2抑制剂鲁索替尼用于CNL和aCML患者中的安全性和有效性。本研究是一项II期的试验,招募了44位患者,包括21位CNL和23位aCML。主要结点是持续治疗6个疗

Blood:鲁索替尼也不能改善预后不良的高危型羟基脲耐受性ET患者的预后

具有高血栓风险的特发性血小板增多症(ET)患者需要细胞还原治疗,特别是羟基尿。但很多患者对羟基尿(HC0RES/INT)有耐药性或不耐受,疾病进展风险增加。MAJIC-ET是一项随机的二期研究,将鲁索替尼(RUX)与HC-RES/INT ET中最佳治疗(BAT)进行比较,结果显示两组患者在血液缓解率或疾病进展率方面没有差异。额外的非MPN驱动突变(NDM)对HC-RES/INT ET患者并发症风险