英国剑桥大学Jimmy Van den Eynden研究组发现，在未经治疗的癌症基因组中缺乏可检测到的新抗原消耗信号。该项研究成果在线发表于11月25日的《自然—遗传学》。

基于HLA亲和力预测，他们注释了人类基因组与HLA结合肽的可翻译性，并筛选了未经治疗的癌症的大型基因组数据集中降低的单核苷酸取代率。

当考虑到基于三核苷酸的突变特征时，由于缺乏动力或肿瘤进化过程中活跃有效的免疫逃逸机制，明显的新抗原耗竭信号变得难以检测。

研究人员表示，体细胞突变可导致新抗原的形成，即由HLA分子呈现在肿瘤细胞表面的免疫原性肽。预计这些突变将处于负选择压力下，但尚不清楚新抗原消耗的程度。

附：英文原文

Title: Lack of detectable neoantigen depletion signals in the untreated cancer genome

Author: Jimmy Van den Eynden, Alejandro Jimnez-Snchez, Martin L. Miller, Erik Larsson

Issue&Volume: 2019-11-25

Abstract: Somatic mutations can result in the formation of neoantigens, immunogenic peptides that are presented on the tumor cell surface by HLA molecules. These mutations are expected to be under negative selection pressure, but the extent of the resulting neoantigen depletion remains unclear. On the basis of HLA affinity predictions, we annotated the human genome for its translatability to HLA binding peptides and screened for reduced single nucleotide substitution rates in large genomic data sets from untreated cancers. Apparent neoantigen depletion signals become negligible when taking into consideration trinucleotide-based mutational signatures, owing to lack of power or to efficient immune evasion mechanisms that are active early during tumor evolution.

DOI: 10.1038/s41588-019-0532-6

Source: https://www.nature.com/articles/s41588-019-0532-6