作者
Rachel Rosenthal, Elizabeth Larose Cadieux, Roberto Salgado, Maise Al Bakir, David A Moore, Crispin T Hiley, Tom Lund, Miljana Tanić, James L Reading, Kroopa Joshi, Jake Y Henry, Ehsan Ghorani, Gareth A Wilson, Nicolai J Birkbak, Mariam Jamal-Hanjani, Selvaraju Veeriah, Zoltan Szallasi, Sherene Loi, Matthew D Hellmann, Andrew Feber, Benny Chain, Javier Herrero, Sergio A Quezada, Jonas Demeulemeester, Peter Van Loo, Stephan Beck, Nicholas McGranahan, Charles Swanton
发表日期
2019/3/28
期刊
Nature
卷号
567
期号
7749
页码范围
479-485
出版商
Nature Publishing Group UK
简介
The interplay between an evolving cancer and a dynamic immune microenvironment remains unclear. Here we analyse 258 regions from 88 early-stage, untreated non-small-cell lung cancers using RNA sequencing and histopathology-assessed tumour-infiltrating lymphocyte estimates. Immune infiltration varied both between and within tumours, with different mechanisms of neoantigen presentation dysfunction enriched in distinct immune microenvironments. Sparsely infiltrated tumours exhibited a waning of neoantigen editing during tumour evolution, indicative of historical immune editing, or copy-number loss of previously clonal neoantigens. Immune-infiltrated tumour regions exhibited ongoing immunoediting, with either loss of heterozygosity in human leukocyte antigens or depletion of expressed neoantigens. We identified promoter hypermethylation of genes that contain neoantigenic mutations as an …
学术搜索中的文章
R Rosenthal, EL Cadieux, R Salgado, MA Bakir… - Nature, 2019