Clin Cancer Res:小剂量二甲双胍对食管癌肿瘤免疫微环境的影响

2020-08-10 MedSci原创 MedSci原创

肿瘤免疫微环境(TIME)对使用免疫检查点抑制剂的癌症免疫治疗反应有重要影响。降糖药二甲双胍可能会影响食管鳞状细胞癌(ESCC)的抗肿瘤免疫力。本研究旨在研究二甲双胍对食管癌肿瘤免疫微环境的影响。。

肿瘤免疫微环境(TIME)对使用免疫检查点抑制剂的癌症免疫治疗反应有重要影响。具体而言,“浸润排除”/“冷”TIME可预示反应不良。降糖药二甲双胍可能会影响食管鳞状细胞癌(ESCC)的抗肿瘤免疫力。

在小剂量二甲双胍(250 mg/天)治疗的II期临床试验中,研究人员分析了配对的治疗前后的食管鳞癌样本,以评估直接抗ESCC的活性和TIME重编程。随后,用小剂量二甲双胍(50 mg/kg/天) 短期(1周)或长期(12周)治疗ESCC小鼠模型。

在临床试验中,小剂量二甲双胍不影响ESCC肿瘤的细胞增殖和凋亡(根据Ki67和caspase-3评估)。但二甲双胍治疗使TIME向“浸润炎性”重编程,增加了浸润CD8+T淋巴细胞和CD20+B淋巴细胞的数量。此外,还观察到肿瘤抑制性(CD11c+)巨噬细胞增多,肿瘤促进性(CD163+)巨噬细胞减少。在体外,二甲双胍增强了巨噬细胞介导的ESCC细胞吞噬作用。

在ESCC小鼠中,二甲双胍短期治疗重编程TIME的方式与在人类中的类似,但长期治疗会进一步使TIME向激活状态转变(如CD4+FoxP3+调节T细胞减少),并抑制ESCC生长。在人和小鼠中,二甲双胍均触发了AMPK激活和STAT3失活,改变了免疫细胞中细胞因子的合成(如TNFα、IFNγ和IL-10)。

总而言之,低剂量二甲双胍可将TIME重编程至激活状态,可能是合适的免疫应答调节剂,值得进一步研究。

原始出处:

Shuhong Wang,et al. Low-Dose Metformin Reprograms the Tumor Immune Microenvironment in Human Esophageal Cancer: Results of a Phase II Clinical Trial. Clin Cancer Res August 4 2020 DOI:10.1158/1078-0432.CCR-20-0113

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    2021-02-24

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    2020-10-08 pyaili
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content=二甲双胍,神药!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Aug 10 20:47:02 CST 2020, time=2020-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=807326, encodeId=da5e80e3261e, content=<a href='/topic/show?id=ccf410109188' target=_blank style='color:#2F92EE;'>#食管癌#</a>增加化疗作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=197, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101091, encryptionId=ccf410109188, topicName=食管癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Aug 10 20:37:23 CST 2020, time=2020-08-10, status=1, ipAttribution=)]
    2020-11-16 lovetcm

    低剂量#二甲双胍#,可以作为#免疫调节剂#,这是最难能可贵的。如果与#化疗#药物联用,二甲双胍还能减轻化疗带来的副作用

    0

  4. 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content=二甲双胍,神药!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Aug 10 20:47:02 CST 2020, time=2020-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=807326, encodeId=da5e80e3261e, content=<a href='/topic/show?id=ccf410109188' target=_blank style='color:#2F92EE;'>#食管癌#</a>增加化疗作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=197, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101091, encryptionId=ccf410109188, topicName=食管癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Aug 10 20:37:23 CST 2020, time=2020-08-10, status=1, ipAttribution=)]
    2020-08-16 ms1000000030437501

    一直想写二甲双胍与肿瘤的文章,看了这篇收益不少。

    0

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content=二甲双胍,神药!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Aug 10 20:47:02 CST 2020, time=2020-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=807326, encodeId=da5e80e3261e, content=<a href='/topic/show?id=ccf410109188' target=_blank style='color:#2F92EE;'>#食管癌#</a>增加化疗作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=197, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101091, encryptionId=ccf410109188, topicName=食管癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Aug 10 20:37:23 CST 2020, time=2020-08-10, status=1, ipAttribution=)]
    2020-08-12 zhouqu_8
  7. 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content=二甲双胍,神药!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Aug 10 20:47:02 CST 2020, time=2020-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=807326, encodeId=da5e80e3261e, content=<a href='/topic/show?id=ccf410109188' target=_blank style='color:#2F92EE;'>#食管癌#</a>增加化疗作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=197, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101091, encryptionId=ccf410109188, topicName=食管癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Aug 10 20:37:23 CST 2020, time=2020-08-10, status=1, ipAttribution=)]
    2020-08-12 njwbhuang

    思路很好

    0

  8. 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  9. 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content=二甲双胍,神药!, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=misszhang, createdTime=Mon Aug 10 20:47:02 CST 2020, time=2020-08-10, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=807326, encodeId=da5e80e3261e, content=<a href='/topic/show?id=ccf410109188' target=_blank style='color:#2F92EE;'>#食管癌#</a>增加化疗作用, beContent=null, objectType=article, channel=null, level=null, likeNumber=197, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=101091, encryptionId=ccf410109188, topicName=食管癌)], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20220519/c2ab253484ee4527a2d4e9589a4821ac/45de9bf494a54becb2ea4369c9d11e85.jpg, createdBy=7a3710, createdName=lovetcm, createdTime=Mon Aug 10 20:37:23 CST 2020, time=2020-08-10, status=1, ipAttribution=)]
    2020-08-10 misszhang

    二甲双胍,神药!

    0

  10. 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    2020-08-10 lovetcm

    #食管癌#增加化疗作用

    0

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