| Literature DB >> 30894752 |
Rachel Rosenthal1,2,3, Elizabeth Larose Cadieux4, Roberto Salgado5,6, Maise Al Bakir3, David A Moore7, Crispin T Hiley1,3, Tom Lund8,9, Miljana Tanić10, James L Reading8,9, Kroopa Joshi8,9, Jake Y Henry8,9, Ehsan Ghorani8,9, Gareth A Wilson1,3, Nicolai J Birkbak1,3, Mariam Jamal-Hanjani1, Selvaraju Veeriah1, Zoltan Szallasi11,12, Sherene Loi6, Matthew D Hellmann13,14, Andrew Feber15, Benny Chain16,17, Javier Herrero2, Sergio A Quezada1,8,9, Jonas Demeulemeester4,18, Peter Van Loo4,18, Stephan Beck10, Nicholas McGranahan19,20, Charles Swanton21,22.
Abstract
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 epigenetic mechanism of immunoediting. Our results suggest that the immune microenvironment exerts a strong selection pressure in early-stage, untreated non-small-cell lung cancers that produces multiple routes to immune evasion, which are clinically relevant and forecast poor disease-free survival.Entities:
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Year: 2019 PMID： 30894752 PMCID： PMC6954100 DOI： 10.1038/s41586-019-1032-7
Source DB: PubMed Journal: Nature ISSN： 0028-0836 Impact factor: 49.962