Nat Commun:从肿瘤形成前到浸润性肺腺癌的免疫进化过程及其潜在的分子特征

2021-05-28 xiaozeng MedSci原创

尽管目前在临床治疗上已取得了令人鼓舞的进步,但是肺癌仍是全球癌症相关死亡的主要原因之一,主要是由无法治愈的晚期诊断所致。

尽管目前在临床治疗上已取得了令人鼓舞的进步,但是肺癌仍是全球癌症相关死亡的主要原因之一,主要是由无法治愈的晚期诊断所致。

计算机断层扫描(CT)指导的肺癌筛查已让肺癌的死亡率降低了26-61%,这强调了该疾病的早期检测和干预对降低肺癌发生率和死亡率的必要性。然而,目前许多关于原发性肺癌预防的随机临床试验的结果仍令人失望。因此,深入了解早期肺癌发生的相关分子机制能够加快该疾病的精确诊断以及有效的预防和治疗策略的发展。


肺腺癌(ADC)是肺癌最常见的组织学亚型,早期肺部ADC及其前体通常以肺结节的形式出现,具有独特的放射性特征,称为毛玻璃不透明性(GGO)。这些肺结节通常被称为不确定的肺结节(IPN),活检对以GGO为主的结节的诊断率很低,且手术切除也不是标准的治疗方法。这也导致了缺乏足够的材料来研究肺ADC前体的分子结构。

目前,关于抗癌免疫力影响ADC早期致癌作用的相关分子机制尚不清楚。


在该研究中,研究人员通过转录组免疫分析、T细胞受体(TCR)测序和多重免疫荧光(mIF)试验来表征侵袭性ADC及其前体的免疫情况。

不同阶段的IPN免疫景观及其相关的基因组和表观基因组特征

结果显示,从肺癌形成到侵袭前病变ADC、微侵袭性ADC以及侵袭性ADC的连续过程中,抗癌免疫力的免疫应答逐渐降低,且该调节强度逐渐增强,包括免疫激活信号的下调、免疫抑制信号的上调、细胞毒性T细胞(CTL)和抗肿瘤辅助性T细胞(Th)浸润的降低、调节性T细胞(Tregs)浸润的升高、T细胞克隆性的降低以及后期阶段里顶端T细胞克隆频率的降低。


驱动子突变、染色体拷贝数畸变(CNA)和异常的DNA甲基化可能共同影响宿主的免疫反应并促进免疫逃逸的发生,并促进新陈代谢中合适的亚克隆向侵袭性ADC中的显性克隆发展。

从瘤前病变到侵袭性肺腺癌的免疫景观

总而言之,该研究结果表明,针对肺癌前体患者的免疫微环境进行治疗,可防止侵袭性肺癌的发展。根据上述的研究发现,在侵袭性肺癌中,在强化免疫抑制之前,重编程ADC前体患者的肿瘤免疫/炎症微环境的治疗策略可能是有益的。


原始出处:

Dejima, H., Hu, X., Chen, R. et al. Immune evolution from preneoplasia to invasive lung adenocarcinomas and underlying molecular features. Nat Commun 12, 2722 (11 May 2021).

 

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    2021-08-27 liye789132251
  4. [GetPortalCommentsPageByObjectIdResponse(id=1771451, encodeId=c0ee1e7145167, content=<a href='/topic/show?id=655b31640c7' target=_blank style='color:#2F92EE;'>#分子特征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31640, encryptionId=655b31640c7, topicName=分子特征)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Thu Aug 19 06:00:25 CST 2021, time=2021-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809088, encodeId=f69018090881c, content=<a href='/topic/show?id=f0f982912b0' target=_blank style='color:#2F92EE;'>#肿瘤形成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82912, encryptionId=f0f982912b0, topicName=肿瘤形成)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=05a2499, createdName=dzx0922889, createdTime=Mon Mar 21 17:00:25 CST 2022, time=2022-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885184, encodeId=f83218851848d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 27 09:00:25 CST 2021, time=2021-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2088002, encodeId=2914208800240, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Mar 15 15:00:25 CST 2022, time=2022-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969863, encodeId=7ac896986321, content=免疫抑制, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTK0iclWFtP7WicKXLyVXAOnRibMria0BwB4otV2d2ibbbkZ2XKAvnNH5x3Y1wm9ibMNZZV5ib5qA0B99sMpw/132, createdBy=9a062530214, createdName=yelinlin, createdTime=Mon May 31 14:37:34 CST 2021, time=2021-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969844, encodeId=712696984494, content=学习这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5cf32976659, createdName=2289576799, createdTime=Mon May 31 13:46:04 CST 2021, time=2021-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969380, encodeId=cc3496938081, content=很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTK0iclWFtP7WicKXLyVXAOnRibMria0BwB4otV2d2ibbbkZ2XKAvnNH5x3Y1wm9ibMNZZV5ib5qA0B99sMpw/132, createdBy=9a062530214, createdName=yelinlin, createdTime=Sat May 29 09:47:53 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969357, encodeId=431896935e8c, content=加快科技进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56245508167, createdName=仔仔斧, createdTime=Sat May 29 09:01:22 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969317, encodeId=ad3896931e96, content=加快科技进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4gCIdSaEkahCNuUWZv4iaKmqvUKHyKnBiarBM9RStQKBeV5Lh6GYYFiamdV5KlSfbLvmAgZTLtq81XA/0, createdBy=13511650672, createdName=言西早, createdTime=Fri May 28 23:29:11 CST 2021, time=2021-05-28, status=1, ipAttribution=)]
    2022-03-15 liuli5079
  5. [GetPortalCommentsPageByObjectIdResponse(id=1771451, encodeId=c0ee1e7145167, content=<a href='/topic/show?id=655b31640c7' target=_blank style='color:#2F92EE;'>#分子特征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31640, encryptionId=655b31640c7, topicName=分子特征)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Thu Aug 19 06:00:25 CST 2021, time=2021-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809088, encodeId=f69018090881c, content=<a href='/topic/show?id=f0f982912b0' target=_blank style='color:#2F92EE;'>#肿瘤形成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82912, encryptionId=f0f982912b0, topicName=肿瘤形成)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=05a2499, createdName=dzx0922889, createdTime=Mon Mar 21 17:00:25 CST 2022, time=2022-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885184, encodeId=f83218851848d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 27 09:00:25 CST 2021, time=2021-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2088002, encodeId=2914208800240, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Mar 15 15:00:25 CST 2022, time=2022-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969863, encodeId=7ac896986321, content=免疫抑制, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTK0iclWFtP7WicKXLyVXAOnRibMria0BwB4otV2d2ibbbkZ2XKAvnNH5x3Y1wm9ibMNZZV5ib5qA0B99sMpw/132, createdBy=9a062530214, createdName=yelinlin, createdTime=Mon May 31 14:37:34 CST 2021, time=2021-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969844, encodeId=712696984494, content=学习这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5cf32976659, createdName=2289576799, createdTime=Mon May 31 13:46:04 CST 2021, time=2021-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969380, encodeId=cc3496938081, content=很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTK0iclWFtP7WicKXLyVXAOnRibMria0BwB4otV2d2ibbbkZ2XKAvnNH5x3Y1wm9ibMNZZV5ib5qA0B99sMpw/132, createdBy=9a062530214, createdName=yelinlin, createdTime=Sat May 29 09:47:53 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969357, encodeId=431896935e8c, content=加快科技进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56245508167, createdName=仔仔斧, createdTime=Sat May 29 09:01:22 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969317, encodeId=ad3896931e96, content=加快科技进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4gCIdSaEkahCNuUWZv4iaKmqvUKHyKnBiarBM9RStQKBeV5Lh6GYYFiamdV5KlSfbLvmAgZTLtq81XA/0, createdBy=13511650672, createdName=言西早, createdTime=Fri May 28 23:29:11 CST 2021, time=2021-05-28, status=1, ipAttribution=)]
    2021-05-31 yelinlin

    免疫抑制

    0

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    2021-05-31 2289576799

    学习这篇文章

    0

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    2021-05-29 yelinlin

    很棒

    0

  8. [GetPortalCommentsPageByObjectIdResponse(id=1771451, encodeId=c0ee1e7145167, content=<a href='/topic/show?id=655b31640c7' target=_blank style='color:#2F92EE;'>#分子特征#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=31640, encryptionId=655b31640c7, topicName=分子特征)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=4c37265, createdName=医者仁心, createdTime=Thu Aug 19 06:00:25 CST 2021, time=2021-08-19, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1809088, encodeId=f69018090881c, content=<a href='/topic/show?id=f0f982912b0' target=_blank style='color:#2F92EE;'>#肿瘤形成#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=42, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=82912, encryptionId=f0f982912b0, topicName=肿瘤形成)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=05a2499, createdName=dzx0922889, createdTime=Mon Mar 21 17:00:25 CST 2022, time=2022-03-21, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1885184, encodeId=f83218851848d, content=<a href='/topic/show?id=3b2112532d8' target=_blank style='color:#2F92EE;'>#Nat#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=33, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=12532, encryptionId=3b2112532d8, topicName=Nat)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=2e6f107, createdName=liye789132251, createdTime=Fri Aug 27 09:00:25 CST 2021, time=2021-08-27, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=2088002, encodeId=2914208800240, content=<a href='/topic/show?id=490750196b' target=_blank style='color:#2F92EE;'>#COMMUN#</a>, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[TopicDto(id=5019, encryptionId=490750196b, topicName=COMMUN)], attachment=null, authenticateStatus=null, createdAvatar=, createdBy=7931272, createdName=liuli5079, createdTime=Tue Mar 15 15:00:25 CST 2022, time=2022-03-15, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969863, encodeId=7ac896986321, content=免疫抑制, beContent=null, objectType=article, channel=null, level=null, likeNumber=62, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTK0iclWFtP7WicKXLyVXAOnRibMria0BwB4otV2d2ibbbkZ2XKAvnNH5x3Y1wm9ibMNZZV5ib5qA0B99sMpw/132, createdBy=9a062530214, createdName=yelinlin, createdTime=Mon May 31 14:37:34 CST 2021, time=2021-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969844, encodeId=712696984494, content=学习这篇文章, beContent=null, objectType=article, channel=null, level=null, likeNumber=0, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=5cf32976659, createdName=2289576799, createdTime=Mon May 31 13:46:04 CST 2021, time=2021-05-31, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969380, encodeId=cc3496938081, content=很棒, beContent=null, objectType=article, channel=null, level=null, likeNumber=48, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=http://thirdwx.qlogo.cn/mmopen/vi_32/Q0j4TwGTfTK0iclWFtP7WicKXLyVXAOnRibMria0BwB4otV2d2ibbbkZ2XKAvnNH5x3Y1wm9ibMNZZV5ib5qA0B99sMpw/132, createdBy=9a062530214, createdName=yelinlin, createdTime=Sat May 29 09:47:53 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969357, encodeId=431896935e8c, content=加快科技进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=46, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=null, createdBy=56245508167, createdName=仔仔斧, createdTime=Sat May 29 09:01:22 CST 2021, time=2021-05-29, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=969317, encodeId=ad3896931e96, content=加快科技进步, beContent=null, objectType=article, channel=null, level=null, likeNumber=41, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://wx.qlogo.cn/mmopen/Q3auHgzwzM4gCIdSaEkahCNuUWZv4iaKmqvUKHyKnBiarBM9RStQKBeV5Lh6GYYFiamdV5KlSfbLvmAgZTLtq81XA/0, createdBy=13511650672, createdName=言西早, createdTime=Fri May 28 23:29:11 CST 2021, time=2021-05-28, status=1, ipAttribution=)]
    2021-05-29 仔仔斧

    加快科技进步

    0

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    2021-05-28 言西早

    加快科技进步

    0

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