Cancer Med:中科院深圳先进院陈志英研究组等构建23个中国妇女早期
近日，美国《Cancer Medicine》杂志在线发表了中国科学院深圳先进技术研究院陈志英团队与华大基因合作的一项癌症研究成果。研究利用癌症基因组学，构建23个中国妇女早期宫颈癌的“癌症抗原树”，目的是帮助找出最佳癌症免疫治疗靶点，以提高疗效。
科学家利用人类基因不断突变、突变可以遗传到后代两大特点，做出人类起源于非洲的结论，并绘制出了走出非洲衍化出不同人种的路线图。除了肤色不同，人类种族间对疾病与治疗的敏感性都有差异。同样，癌症起源于一个细胞，是基因突变积累的结果，这些突变产生很多新靶点，成为癌细胞独有且理想的治疗靶点，不会伤及正常细胞。由于突变不断发生，衍生出许多细胞群，不同细胞群有不同的靶点组合，对治疗的反应也不同。目前的免疫治疗技术，大多只针对部分细胞群，对于实体瘤来说，临床上可使肿瘤缩小、病情稳定，但残留癌细胞群继续生长，不久又复发。
“癌症抗原树”是团队开发的新电子计算机算法，根据癌症基因组学的资料，找出一个癌症内所有细胞群及其靶点之间的进化关系，帮助确定“树干”上所有癌细胞共有的靶点，大大提高疗效。该算法对指导发展新一代癌症免疫治疗技术有重要指导意义。该项目是团队构建中的“微环DNA基因载体癌症免疫治疗技术平台”的一个组成部分，旨在开发出安全、高效、方便、可负担的抗癌基因药。
图为癌症免疫抗原树：A. 人类走出非洲并衍化出不同种族的路线图;B.“癌症抗原树”描绘肿瘤细胞群及其携带的肿瘤抗原的相互关系;C.“癌症抗原树”帮助找出“树干”上的靶点，像砍树干把树砍死一样，高效治疗肿瘤;D. 三个代表性宫颈癌抗原树
原文链接：
Whole-exome sequencing predicted cancer epitope trees of 23 early cervical cancers in Chinese women.
原文摘要：
Emerging evidence suggest that the heterogeneity of cancer limits the efficacy of immunotherapy. To search for optimal therapeutic targets for enhancing the efficacy, we used whole-exome sequencing data of 23 early cervical tumors from Chinese women to investigate the hierarchical structure of the somatic mutations and the neo-epitopes. The putative neo-epitopes were predicted based on the mutant peptides’ strong binding with major histocompatibility complex class I molecules. We found that each tumor carried an average of 117 mutations and 61 putative neo-epitopes. Each patient displayed a unique phylogenetic tree in which almost all subclones harbored neo-epitopes, highlighting the importance of individual neo-epitope tree in determination of immunotherapeutic targets. The alterations in FBXW7 and PIK3CA, or other members of the significantly altered ubiquitin-mediated proteolysis and extracellular matrix receptor interaction related pathways, were proposed as the earliest changes triggering the malignant progression. The neo-epitopes involved in these pathways, and located at the top of the hierarchy tree, might become the optimal candidates for therapeutic targets, possessing the potential to mediate T-cell killing of the descendant cells. These findings expanded our understanding in early stage of cervical carcinogenesis and offered an important approach to assist optimizing the immunotherapeutic target selection.
作者：陈志英
