Lancet Oncology:人体内有那么多微生物,它们对癌症的发生和治疗有哪些影响?

2020-08-02 佚名 医学新视点

人体微生物组与我们共同进化、共同生存,也与我们的健康有着复杂联系。比如我们常说的肠道菌群,其多样性和构成情况,对每个人来说都是独特的健康相关特征。今年探索了很多人体不同组织内的微生物与癌症的关联。

人体微生物组与我们共同进化、共同生存,也与我们的健康有着复杂联系。比如我们常说的肠道菌群,其多样性和构成情况,对每个人来说都是独特的健康相关特征。而放眼消化道以外,人体不同组织内的微生物与癌症的关联,近年来也得到了更多探索。《柳叶刀-肿瘤学》7月刊上的一篇文章就针对这个有趣的主题,简要盘点了当前研究进展。

预测免疫疗法的疗效

随着免疫疗法,尤其是抗PD-1/PD-L1、抗CTLA-4等免疫检查点抑制剂疗法如火如荼的发展,人们也观察到一个现象:这些创新疗法为癌症治疗带来了变革,但只有部分患者对免疫疗法有反应。为了识别有潜力从中获益的患者,对生物标志物的探索发现,肠道微生物是潜在线索之一。

越来越多研究数据显示,患者的肠道微生物组特征与接受免疫疗法后的疗效反应或毒副作用反应相关。2018年,“肠道菌群与癌症”曾荣登《科学》(Science)封面。

其中的一项研究来自MD安德森癌症中心团队,在接受抗PD-1免疫疗法的黑色素瘤患者中,对治疗有反应者和无反应者在肠道微生物组的多样性和构成上有着显着差异。有反应者的粪便微生物组样本中,Ruminococcaceae科细菌的丰度更高、体内的合成代谢通路更为丰富,系统免疫力与抗肿瘤免疫力也更强。

更值得关注的是,肠道微生物组与治疗反应的这种关联是有望被调节的。MD安德森癌症中心团队在2019年美国癌症研究协会(AACR)年会上带来的另一项研究也显示,通过对肠道菌群的影响,日常饮食也可能会影响抗PD-1疗法的效果。而服用益生菌补充剂或使用抗生素的患者,其肠道微生物组多样性则比较差,尤其是益生菌可能会间接影响治疗效果。

不过,现有研究对肠道菌群的DNA测序大多限于“属”的水平,限制了进一步探索特定细菌菌株与患者对免疫治疗反应的关联。为了提供在分类学上更为精细的数据,英国Microbiotica公司、英国癌症研究中心和剑桥大学医院NHS信托基金会在今年6月启动合作,计划通过两项大型试验开展癌症微生物组研究,旨在鉴定出有益免疫疗法效果的微生物组并开发微生物组疗法作为伴随治疗。其中一项名为MITRE的试验计划在英国招募1800名黑色素瘤、肺癌和肾癌患者。

对常见化疗的效果可能也有影响

除了免疫疗法,新兴证据表明,患者对传统化疗的反应也可能受到肠道菌群和饮食相互作用的调节。

今年5月发表在《自然-通讯》(Nature Communications)的一项动物实验显示,在线虫中,饮食成分胸苷和丝氨酸可以通过微生物代谢机制而增强氟尿嘧啶类药物的毒性反应。其中,大肠杆菌对叶酸的代谢是影响药物毒性的关键因素。在消化道癌症的治疗中,氟尿嘧啶是化疗方案的主要组成。

虽然相较于哺乳动物实验,线虫是比较简单的实验模型,但所观察到的微生物、饮食和宿主与治疗药物之间的这种相互作用,提示了实际在人类患者中,微生物组参与的疗效影响可能更为复杂。

肿瘤中也有微生物生长

同时,科学家们也越来越认识到,同样生长在人体内的肿瘤,本身也可能是微生物的宿主。

以色列魏兹曼科学研究院(Weizmann Institute of Science)团队前不久在《科学》(Science)发表的研究,对7种癌症共1526份人类肿瘤或临近组织样本的微生物组进行了评估。结果发现,每种肿瘤类型的样本都有独特的微生物组构成,其中乳腺癌中的微生物组成尤为丰富,每个乳腺肿瘤样本平均有16.4种细菌,而其他6种肿瘤单个样本中细菌则少于9种。研究团队观察到,这些细菌大多存在于细胞内部,包括癌细胞和免疫细胞。

更有意思的是,这些细菌或其潜在功能,与肿瘤类型、患者吸烟状况以及对免疫疗法的反应都有所关联。比如,在任何特定类型肿瘤中,单个肿瘤样本中的菌群有着惊人的相似性。再比如,与非吸烟者相比,吸烟者的非小细胞肺癌组织样本似乎富含能够降解卷烟化学物质的细菌。

对此,澳大利亚Olivia Newton-John癌症研究所Andreas Behren博士认为,“这项研究证明了,关于细菌在肿瘤中的潜在作用,以及细菌如何影响肿瘤微环境,我们仍有许多有待了解。这项研究也启发了我们探索先天免疫与癌症免疫的关联。”

将微生物组作为改善人类健康的治疗手段,是诸多研究期待解决的问题之一。从感染、炎症性疾病乃至肥胖等代谢性疾病,已经有了一些初步探索的成果。期待在癌症领域,在这些洞见的推动下,微生物组的功能也能得到更深入的理解,早日为癌症诊疗带来全新策略。

原始出处:

Ashray Gunjur. Cancer and the microbiome. The Lancet Oncology,Volume 21, Issue 7, July 2020, Page 888. DOI: 10.1016/S1470-2045(20)30351-X

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    2021-01-24 minlingfeng
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    2020-11-13 howi
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  5. [GetPortalCommentsPageByObjectIdResponse(id=1825183, encodeId=96ce1825183e4, content=<a href='/topic/show?id=702a5065860' target=_blank style='color:#2F92EE;'>#微生物#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=50658, encryptionId=702a5065860, topicName=微生物)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=0b7c20, createdName=wjcjjian, createdTime=Mon Oct 26 09:15:22 CST 2020, time=2020-10-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1865875, encodeId=249218658e595, content=<a href='/topic/show?id=16ce133504e' target=_blank style='color:#2F92EE;'>#Oncol#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13350, encryptionId=16ce133504e, topicName=Oncol)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=b63894, createdName=minlingfeng, createdTime=Sun Jan 24 08:15:22 CST 2021, time=2021-01-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1830766, encodeId=1c071830e66f9, content=<a href='/topic/show?id=1b6210686b2' target=_blank style='color:#2F92EE;'>#Lancet#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=47, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=10686, encryptionId=1b6210686b2, topicName=Lancet)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=3f0227, createdName=howi, createdTime=Fri Nov 13 02:15:22 CST 2020, time=2020-11-13, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1674477, encodeId=270f16e44776f, content=<a href='/topic/show?id=e8aa13359b1' target=_blank style='color:#2F92EE;'>#Oncology#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=49, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=13359, encryptionId=e8aa13359b1, topicName=Oncology)], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=cb7226973259, createdName=circumcision, createdTime=Wed Mar 24 11:15:22 CST 2021, time=2021-03-24, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=805894, encodeId=95f2805894c1, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=126, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200803/d669a8255ef042b4b50cb4b323fac1e4/3da0f519fc71432ca9a2f4c05279c082.jpg, createdBy=a8312408082, createdName=chenny, createdTime=Mon Aug 03 12:17:57 CST 2020, time=2020-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=805857, encodeId=9cc580585edd, content=学习了,谢谢分享, beContent=null, objectType=article, channel=null, level=null, likeNumber=95, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7c592194322, createdName=1209e435m98(暂无昵称), createdTime=Mon Aug 03 06:30:48 CST 2020, time=2020-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=805849, encodeId=a0a3805849c4, content=学习, beContent=null, objectType=article, channel=null, level=null, likeNumber=104, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20200804/62f3c5bb78aa4f1bac3aef7bcd9c1c0d/029c3f00f77d40db887fd7feb647c9ef.jpg, createdBy=c8e65408461, createdName=月瘦如眉, createdTime=Mon Aug 03 06:21:20 CST 2020, time=2020-08-03, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1033910, encodeId=f6081033910f0, content=顶刊就是不一样,质量很高,内容精彩!学到很多, beContent=null, objectType=article, channel=null, level=null, likeNumber=57, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=goodbing, createdTime=Sun Aug 02 13:15:22 CST 2020, time=2020-08-02, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1038077, encodeId=a2da10380e7cf, content=谢谢梅斯分享这么多精彩信息, beContent=null, objectType=article, channel=null, level=null, likeNumber=52, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=f0620, createdName=anti-cancer, createdTime=Sun Aug 02 13:15:22 CST 2020, time=2020-08-02, status=1, ipAttribution=)]
    2020-08-03 chenny

    学习了,谢谢分享

    0

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    2020-08-03 1209e435m98(暂无昵称)

    学习了,谢谢分享

    0

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    2020-08-03 月瘦如眉

    学习

    0

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    2020-08-02 goodbing

    顶刊就是不一样,质量很高,内容精彩!学到很多

    0

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    2020-08-02 anti-cancer

    谢谢梅斯分享这么多精彩信息

    0

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