Immunity:发现改善化学治疗抗肿瘤效果新机制

2019-02-16 辉宏俊 iNature

肿瘤是一种基因病,但并非是遗传的。它是指细胞在致癌因素作用下,基因发生了改变,失去对其生长的正常调控,导致单克隆性异常增生而形成的新生物。全身免疫抑制极大地影响化学治疗抗肿瘤作用。2019年2月12日,由浙江大学医学院蔡志坚&王建莉组成的团队在Immunity上发表了题为“Specific Decrease inB-Cell-Derived Extracellular Vesicles Enhan

肿瘤是一种基因病,但并非是遗传的。它是指细胞在致癌因素作用下,基因发生了改变,失去对其生长的正常调控,导致单克隆性异常增生而形成的新生物。全身免疫抑制极大地影响化学治疗抗肿瘤作用。2019年2月12日,由浙江大学医学院蔡志坚&王建莉组成的团队在Immunity上发表了题为“Specific Decrease inB-Cell-Derived Extracellular Vesicles Enhances Post-Chemotherapeutic CD8 +T Cell Responses”的研究论文。该论文表明:降低CD19 + EV具有改善化学治疗抗肿瘤效果的高潜力。

化疗仍然是晚期癌症最经典的治疗方法之一。一些化疗药物是重新通过消除免疫抑制细胞或引发肿瘤细胞的“免疫原性细胞死亡”来提高抗肿瘤免疫力然而,化疗长期以来一直与全身免疫抑制的诱导有关。许多化学治疗剂是骨髓抑制剂,可以抑制骨髓中血细胞的产生,减少绝对的白细胞计数,导致淋巴细胞增多。因此,化疗后改善全身免疫抑制是改善化疗后抗肿瘤免疫力所必需的。

研究人员显示来自B细胞的CD19+细胞外囊泡(EV)通过CD39和CD73囊泡掺入的蛋白质将化学治疗的肿瘤细胞中的ATP水解成腺苷,从而损害CD8 + T细胞应答。携带肿瘤的小鼠和患者的血清CD19+ EVs增加。血清CD19 + EV较少的患者化疗后预后较好。上调的缺氧诱导因子-1α(HIF-1α)通过诱导Rab27a mRNA转录促进B细胞释放CD19+ EV。 B细胞中Rab27a或HIF-1α缺乏抑制CD19+EV产生并改善化学治疗抗肿瘤作用。

通过携带Rab27a siRNA的灭活的Epstein-Barr病毒沉默B细胞中的Rab27a极大地改善了人源化免疫妥协的NOD Prkdc scid Il2rg - / - 小鼠的化学疗效。因此,降低CD19 + EV具有改善化学治疗抗肿瘤效果的高潜力。

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  3. [GetPortalCommentsPageByObjectIdResponse(id=2030391, encodeId=01a82030391be, content=<a href='/topic/show?id=25079e7287' target=_blank style='color:#2F92EE;'>#Immunity#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=9772, encryptionId=25079e7287, topicName=Immunity)], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/C4Qhy5XHSe503Qbjzc1UtDR83BCv66o6P2XRedX9ohsNGa3uEVicFFk2qkuX5zBSmpicepFySBrwoYknhqMdKmtw/132, createdBy=1aca2500179, createdName=12498d2fm51(暂无昵称), createdTime=Fri Nov 01 14:51:00 CST 2019, time=2019-11-01, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1989698, encodeId=8ca019896985d, content=<a href='/topic/show?id=8e5c33503d1' target=_blank style='color:#2F92EE;'>#化学治疗#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=26, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=33503, encryptionId=8e5c33503d1, topicName=化学治疗)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=6c32257, createdName=DEXTER3139, createdTime=Mon Jun 17 16:51:00 CST 2019, time=2019-06-17, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1046747, encodeId=a1491046e479b, content=疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的, beContent=null, objectType=article, channel=null, level=null, likeNumber=58, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=CHANGE, createdTime=Sat Feb 16 13:51:00 CST 2019, time=2019-02-16, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=360777, encodeId=d30d360e77b3, content=点赞!认真学习了,把经验应用于实践,为患者解除病痛。, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/mStl88fu4NfNLvzZhgPxRuUXgacXpPeW0x8Z3Qr9c3I2kTic4ZIpR29iaftYgkjRcbv982icYMtqANBPYBgPnOia6mVtX76qMXuc/0, createdBy=ebe61630855, createdName=1dd8a7c5m95(暂无匿称), createdTime=Sat Feb 16 11:02:33 CST 2019, time=2019-02-16, status=1, ipAttribution=)]
    2019-02-16 CHANGE

    疗效只是效果的众多方面之一,还要看对患者的获益,包括生活质量等因素共同决定效果的

    0

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    2019-02-16 1dd8a7c5m95(暂无匿称)

    点赞!认真学习了,把经验应用于实践,为患者解除病痛。

    0

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