小柯机器人

荷兰乌得勒支大学医学中心Edwin Cuppen和Francisco Martínez-Jiménez共同合作，近期取得重要工作进展。他们研究提出了原发性和转移性癌症的遗传免疫逃逸概况。相关研究成果2023年5月10日在线发表于《自然—遗传学》杂志上。

据介绍，近年的研究已经表征了原发性肿瘤的免疫逃逸概况。然而，晚期转移瘤在遗传免疫逃逸（GIE）患病率和动力学方面是否存在差异仍不清楚。

研究人员对6319个经过统一处理的肿瘤样本六条免疫逃逸途径中的GIE流行率进行了泛癌特征分析。为了解决种系和肿瘤中HLA-I基因座的复杂性，研究人员开发了一个开源的综合框架LILAC。四分之一的肿瘤具有GIE改变，在癌症类型中具有较高的机械性和频率可变性。原发性和转移性肿瘤之间的GIE患病率通常是一致的。研究人员发现，肿瘤演化中选择了GIE改变，HLA-I杂合性的局灶性丧失往往会消除HLA等位基因，呈现出最大的新表位库。最后，高突变负荷肿瘤显示出作为免疫逃避机制的HLA-I杂合性的局灶性丧失的趋势，而在高突变肿瘤中，其它免疫逃避策略占主导地位。

附：英文原文

Title: Genetic immune escape landscape in primary and metastatic cancer

Author: Martnez-Jimnez, Francisco, Priestley, Peter, Shale, Charles, Baber, Jonathan, Rozemuller, Erik, Cuppen, Edwin

Issue&Volume: 2023-05-10

Abstract: Studies have characterized the immune escape landscape across primary tumors. However, whether late-stage metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. We performed a pan-cancer characterization of GIE prevalence across six immune escape pathways in 6,319 uniformly processed tumor samples. To address the complexity of the HLA-I locus in the germline and in tumors, we developed LILAC, an open-source integrative framework. One in four tumors harbors GIE alterations, with high mechanistic and frequency variability across cancer types. GIE prevalence is generally consistent between primary and metastatic tumors. We reveal that GIE alterations are selected for in tumor evolution and focal loss of heterozygosity of HLA-I tends to eliminate the HLA allele, presenting the largest neoepitope repertoire. Finally, high mutational burden tumors showed a tendency toward focal loss of heterozygosity of HLA-I as the immune evasion mechanism, whereas, in hypermutated tumors, other immune evasion strategies prevail.

DOI: 10.1038/s41588-023-01367-1

Source: https://www.nature.com/articles/s41588-023-01367-1

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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投稿链接：https://mts-ng.nature.com/cgi-bin/main.plex