揭秘肿瘤细胞与免疫细胞的对战,复旦中山医院携手华大为最难治疗的肿瘤供给治疗新策略
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_gif/DYM6qrjnictaWln83zgVmGfaNP46jcUkAnON4CaDQ5jASRmvdnbtXj3stX8xIv5W18bXt16JFsxdXdsbNTxw52w/640?wx_fmt=gif&tp=webp&wxfrom=5&wx_lazy=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">说到</span>肝癌,<span style="color: black;">大众</span>都不陌生。它在新发性癌症和致死性癌症榜单中都名列前五。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">而<span style="color: black;">博主</span>今天想和你聊的<strong style="color: blue;"><span style="color: black;">肝内胆管癌</span></strong>,是第二大原发性肝癌,<span style="color: black;">亦</span>是预后最差的肿瘤之一,大部分<span style="color: black;">病人</span>在确诊时已<span style="color: black;">处在</span>晚期,<span style="color: black;">日前</span>仍缺乏有效的治疗手段。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">为何</span>它的治疗这么难?</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">由于</span>它发病隐匿,侵袭性强,<span style="color: black;">况且</span>不同<span style="color: black;">病人</span>的肿瘤异质性极高。已有的<span style="color: black;">科研</span><span style="color: black;">发掘</span>,不仅不同的<span style="color: black;">病人</span><span style="color: black;">拥有</span>不同的免疫微环境,<span style="color: black;">乃至</span>同个<span style="color: black;">病人</span>的病灶中不同区域的肿瘤微环境<span style="color: black;">亦</span>大有不同,这<span style="color: black;">亦</span>是肝内胆管癌肿瘤耐药的<span style="color: black;">重点</span><span style="color: black;">原由</span>之一。<span style="color: black;">因此</span>,<span style="color: black;"><strong style="color: blue;"><span style="color: black;">认识</span>免疫微环境对治疗<span style="color: black;">拥有</span><span style="color: black;">重要</span><span style="color: black;">功效</span></strong></span>。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">近期</span>,复旦大学<span style="color: black;">附庸</span>中山医院联合深圳华大生命科学<span style="color: black;">科研</span>院(以下简<span style="color: black;">叫作</span>“华大<span style="color: black;">科研</span>院”)在Cancer Discovery(影响因子:38.272)上<span style="color: black;">发布</span>最新成果,基于来自45例<span style="color: black;">病人</span>的207份肝内胆管癌多区域样本,整合全外显子测序、转录组测序、TCR测序及多色组化等技术,<span style="color: black;"><strong style="color: blue;">揭示了肿瘤细胞和免疫微环境的互作规律,为肝内胆管癌<span style="color: black;">精细</span>的个体化免疫联合治疗带来了新<span style="color: black;">期盼</span></strong></span>。</p><img src="https://mmbiz.qpic.cn/mmbiz_png/DYM6qrjnictadS15wqBj7BLiaHKSVGoRa19VuRcugE2VTzKt2FnKV4qI4ZL9Oa8Jq1ATT0oXKtC6MKuqQl4NND2w/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">Cancer Discovery </span><span style="color: black;">官网截图</span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">肿瘤其实并不<span style="color: black;">仅有</span>肿瘤细胞,它就像一个战场,<span style="color: black;">同期</span>还<span style="color: black;">包括</span>了浸润的免疫细胞、间质细胞和微血管等,<span style="color: black;">咱们</span><span style="color: black;">亦</span><span style="color: black;">叫作</span>之为肿瘤免疫微环境。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">在这个“战场”里,免疫细胞会针对性地识别肿瘤细胞,并将其清除掉。<span style="color: black;">然则</span>,肿瘤细胞<span style="color: black;">亦</span>不是这么好欺负的,它会<span style="color: black;">经过</span><span style="color: black;">各样</span>手段,躲避免疫细胞的“围剿”,<span style="color: black;">最后</span>肆意生长(<span style="color: black;">咱们</span>把这个过程叫做免疫逃逸)。不同肿瘤<span style="color: black;">拥有</span>不同的免疫微环境特点和免疫逃逸机制,对免疫治疗产生不同潜在效果。</p><img src="https://mmbiz.qpic.cn/mmbiz_jpg/DYM6qrjnictadS15wqBj7BLiaHKSVGoRa1tco9onwHDDcVd5AjI9hhTBYHtibaUwUppuCtewibjDw9rC3sA6ZNul8g/640?wx_fmt=jpeg&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">为了阐明免疫微环境是<span style="color: black;">怎样</span>影响肝内胆管癌的发展进程,<span style="color: black;">认识</span>肿瘤细胞和免疫细胞“相爱相杀”的过程,促进肝内胆管癌个体化靶向和免疫治疗的<span style="color: black;">科研</span>,<span style="color: black;">科研</span>者对<span style="color: black;">以上</span>45位<span style="color: black;">病人</span>手术切除的肝内胆管癌样本进行了多区域取样(每位<span style="color: black;">病人</span><span style="color: black;">选择</span>4-6个区域),利用免疫基因组学分析<span style="color: black;">发掘</span>,<span style="color: black;"><strong style="color: blue;">肝内胆管癌不仅在基因组水平表现出极高的肿瘤内异质性,并且在免疫微环境水平<span style="color: black;">亦</span>存在巨大差异。</strong></span><span style="color: black;">因此呢</span>,<span style="color: black;">按照</span><span style="color: black;">病人</span>病灶中的浸润免疫细胞含量,<span style="color: black;">科研</span>者将<span style="color: black;">病人</span>分为了三种免疫类型:<span style="color: black;"><strong style="color: blue;">低免疫浸润</strong></span>、<span style="color: black;"><strong style="color: blue;">高免疫浸润</strong></span>和<span style="color: black;"><strong style="color: blue;">异质性免疫浸润</strong></span>,并且<span style="color: black;">按照</span>这三种类型的特点,给出了<span style="color: black;">意见</span>的免疫治疗方式:<img src="https://mmbiz.qpic.cn/mmbiz_png/uEpNIfeSkS2cWpK9Z7OMicNicvkicicCYgQygup93hkjYXsVVNIqIVz19yMX5KmEAkx6nBvqHeWjjXX5KmFrLLRq2Q/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">类型一:高免疫浸润肿瘤</p><img src="https://mmbiz.qpic.cn/mmbiz_png/zqFgibAAQ9KN5UIFhicMP3BsKibEh9LK40gUbkm0kKLyCuiccVejNRSyP11Ve1kyPo6XtnPTOOas9VMDfKYx8iaIKFg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">疲惫的免疫细胞 VS “狡猾”的肿瘤细胞</span><strong style="color: blue;"><span style="color: black;">特征:</span></strong><span style="color: black;">这类型<span style="color: black;">病人</span>的肿瘤虽然浸润较多<span style="color: black;">拥有</span>杀伤能力的免疫细胞,但却有<span style="color: black;">海量</span>的免疫细胞<span style="color: black;">显现</span>疲惫状态(细胞耗竭),发挥不出本来的免疫杀伤功能,<span style="color: black;">同期</span>,肿瘤细胞还很“狡猾”,<span style="color: black;">经过</span>“变装”(人类白细胞抗原等位基因杂合性缺失和抗原呈递<span style="color: black;">关联</span>基因的拷贝数丢失),使<span style="color: black;">自己</span><span style="color: black;">不易</span>被免疫系统识别。</span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">意见</span>治疗方式:</span></strong><span style="color: black;">免疫治疗<span style="color: black;">协同</span>化疗为主的联合治疗方式。</span><img src="https://mmbiz.qpic.cn/mmbiz_png/uEpNIfeSkS2cWpK9Z7OMicNicvkicicCYgQygup93hkjYXsVVNIqIVz19yMX5KmEAkx6nBvqHeWjjXX5KmFrLLRq2Q/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">类型二:低免疫浸润肿瘤</p><img src="https://mmbiz.qpic.cn/mmbiz_png/zqFgibAAQ9KN5UIFhicMP3BsKibEh9LK40gUbkm0kKLyCuiccVejNRSyP11Ve1kyPo6XtnPTOOas9VMDfKYx8iaIKFg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;">肿瘤细胞来势凶猛 免疫细胞“兵力”不足</span><strong style="color: blue;"><span style="color: black;">特征:</span></strong><span style="color: black;">肿瘤样本含有<span style="color: black;">海量</span>的恶性肿瘤细胞,<span style="color: black;">然则</span>免疫细胞含量<span style="color: black;">尤其</span>少,呈现“兵力”不足。<span style="color: black;">同期</span>,肿瘤细胞<span style="color: black;">经过</span>另一种形式的“变装”(主克隆新抗原拷贝数的主动丢失),使免疫细胞难以<span style="color: black;">发掘</span>自己,<span style="color: black;">最后</span>放任肿瘤细胞的生长。</span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">意见</span>治疗方式:</span></strong><span style="color: black;"><span style="color: black;">必须</span>相应的靶向治疗联合免疫治疗。</span><img src="https://mmbiz.qpic.cn/mmbiz_png/uEpNIfeSkS2cWpK9Z7OMicNicvkicicCYgQygup93hkjYXsVVNIqIVz19yMX5KmEAkx6nBvqHeWjjXX5KmFrLLRq2Q/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;">
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">类型三:异质性免疫浸润肿瘤</p><img src="https://mmbiz.qpic.cn/mmbiz_png/zqFgibAAQ9KN5UIFhicMP3BsKibEh9LK40gUbkm0kKLyCuiccVejNRSyP11Ve1kyPo6XtnPTOOas9VMDfKYx8iaIKFg/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"><span style="color: black;"><span style="color: black;">同期</span>具备以上两种<span style="color: black;">状况</span></span><strong style="color: blue;"><span style="color: black;">特征:</span></strong><span style="color: black;">存在高免疫浸润的区域和低免疫浸润的区域,环境更为<span style="color: black;">繁杂</span>,<span style="color: black;">同期</span>,肿瘤细胞采用了主克隆新抗原表达沉默的策略来逃避免疫细胞的识别(对,这是肿瘤细胞第三种形式的“变装”)。</span><strong style="color: blue;"><span style="color: black;"><span style="color: black;">意见</span>治疗方式:</span></strong><span style="color: black;">免疫治疗<span style="color: black;">协同</span>表观调节剂的联合治疗方式。</span>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">另一</span>,综合以上肿瘤的免疫逃逸机制特点,<span style="color: black;">科研</span>者将肝内胆管癌分为了<span style="color: black;"><strong style="color: blue;">免疫低逃逸</strong></span>和<strong style="color: blue;"><span style="color: black;">免疫高逃逸</span></strong>两组,肿瘤免疫逃逸能力强(高逃逸)的<span style="color: black;">病人</span>预后更差,这在<span style="color: black;">日前</span>已有数据库CPTAC和TCGA肝内胆管癌队列中均得到验证,为肝内胆管癌的预后分型<span style="color: black;">供给</span>了新的视角,助力<span style="color: black;">病人</span>预后预测。</p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><img src="https://mmbiz.qpic.cn/mmbiz_png/DYM6qrjnictadS15wqBj7BLiaHKSVGoRa17YS1EpQCQ2MZGvaHhaic57gxnC8KtgC4hbSiauW8SxttaytlazUGfBpQ/640?wx_fmt=png&tp=webp&wxfrom=5&wx_lazy=1&wx_co=1" style="width: 50%; margin-bottom: 20px;"></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;">综上,<span style="color: black;"><strong style="color: blue;">本项<span style="color: black;">科研</span>描绘了肝内胆管癌的肿瘤免疫微环境的相互<span style="color: black;">功效</span>过程,揭示了基因突变对免疫微环境的影响以及免疫微环境中的逃逸机制,为不同类型<span style="color: black;">病人</span>的治疗<span style="color: black;">供给</span>方向,为新型免疫治疗策略的<span style="color: black;">研发</span><span style="color: black;">供给</span>了新的线索。</strong></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;"><span style="color: black;">复旦大学<span style="color: black;">附庸</span>中山医院高强教授、华大<span style="color: black;">科研</span>院吴逵副<span style="color: black;">科研</span>员和复旦大学<span style="color: black;">附庸</span>中山医院樊嘉院士为本文<span style="color: black;">一起</span>通讯作者。复旦中山医院博士生林友培、华大<span style="color: black;">科研</span>院生物信息副<span style="color: black;">科研</span>员彭丽花、复旦中山医院董良庆博士、华大<span style="color: black;">科研</span>院生物信息副<span style="color: black;">科研</span>员刘栋兵为本文<span style="color: black;">一起</span><span style="color: black;">第1</span>作者。</span></span></p>
<p style="font-size: 16px; color: black; line-height: 40px; text-align: left; margin-bottom: 15px;"><span style="color: black;">*点击文末“</span><strong style="color: blue;"><span style="color: black;">阅读原文</span></strong><span style="color: black;">”,查看<span style="color: black;">文案</span>链接</span></p><span style="color: black;">让我<span style="color: black;">晓得</span>你“在看”</span><img src="https://mmbiz.qpic.cn/mmbiz_gif/DYM6qrjnictYmwDMIvjw3fHTpHTibdsbWIbNfP6ldKkZ9fOCQIibx8kszxvIIqXgI48TTUywicI6YB8ePdDBr6WflA/640?wx_fmt=gif&tp=webp&wxfrom=5&wx_lazy=1" style="width: 50%; margin-bottom: 20px;">
你的见解真是独到,让我受益匪浅。 感谢你的精彩评论,为我的思绪打开了新的窗口。 期待与你深入交流,共探知识的无穷魅力。 你的话语如春风拂面,温暖了我的心房,真的很感谢。
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