Neoantigen-directed immune escape in lung cancer evolution Journal Article
| Authors: | Rosenthal, R.; Cadieux, E. L.; Salgado, R.; Al Bakir, M.; Moore, D. A.; Hiley, C. T.; Lund, T.; Tanić, M.; Reading, J. L.; Joshi, K.; Henry, J. Y.; Ghorani, E.; Wilson, G. A.; Birkbak, N. J.; Jamal-Hanjani, M.; Veeriah, S.; Szallasi, Z.; Loi, S.; Hellmann, M. D.; Feber, A.; Chain, B.; Herrero, J.; Quezada, S. A.; Demeulemeester, J.; Van Loo, P.; Beck, S.; McGranahan, N.; Swanton, C.; The TRACERx consortium |
| Article Title: | Neoantigen-directed immune escape in lung cancer evolution |
| 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. © 2019, The Author(s), under exclusive licence to Springer Nature Limited. |
| Keywords: | survival; cancer survival; controlled study; human tissue; aged; unclassified drug; gene mutation; major clinical study; methylation; mutation; disease course; histopathology; disease free survival; cancer staging; antigen expression; cd8+ t lymphocyte; tumor associated leukocyte; cohort analysis; tumor antigen; immune response; antigen; epigenetics; heterozygosity; gene repression; microenvironment; immunity; lymphocytic infiltration; tumor; lymphocyte count; rna sequence; non small cell lung cancer; cell; tumor microenvironment; copy number variation; immunoediting; tumor escape; rna editing; cancer prognosis; immunological procedures; immune infiltration; cancer; human; male; female; priority journal; article; immune microenvironment; neoantigen |
| Journal Title: | Nature |
| Volume: | 567 |
| Issue: | 7749 |
| ISSN: | 0028-0836 |
| Publisher: | Nature Publishing Group |
| Date Published: | 2019-03-28 |
| Start Page: | 479 |
| End Page: | 485 |
| Language: | English |
| DOI: | 10.1038/s41586-019-1032-7 |
| PUBMED: | 30894752 |
| PROVIDER: | scopus |
| PMCID: | PMC6954100 |
| DOI/URL: | |
| Notes: | Source: Scopus |
