Rosenthal, R., Cadieux, E.L., Salgado, R. et al. (25 more authors) (2019) Neoantigen-directed immune escape in lung cancer evolution. Nature, 567 (7749). pp. 479-485. ISSN 0028-0836
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.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2019, The Author(s). |
Keywords: | Adenocarcinoma; Antigen Presentation; Antigens, Neoplasm; Carcinoma, Non-Small-Cell Lung; Carcinoma, Squamous Cell; Disease-Free Survival; Evolution, Molecular; Female; Gene Expression Regulation, Neoplastic; Humans; Lung Neoplasms; Lymphocytes, Tumor-Infiltrating; Male; Prognosis; Tumor Escape; Tumor Microenvironment |
Dates: |
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Institution: | The University of Sheffield |
Academic Units: | The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine and Population Health The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > The Medical School (Sheffield) > Division of Genomic Medicine (Sheffield) > Department of Oncology and Metabolism (Sheffield) |
Depositing User: | Symplectic Sheffield |
Date Deposited: | 14 Jan 2025 11:25 |
Last Modified: | 14 Jan 2025 11:25 |
Status: | Published |
Publisher: | Springer Science and Business Media LLC |
Refereed: | Yes |
Identification Number: | 10.1038/s41586-019-1032-7 |
Related URLs: | |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:221483 |