Cargando…
Genetic immune escape landscape in primary and metastatic cancer
Studies have characterized the immune escape landscape across primary tumors. However, whether late-stage metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. We performed a pan-cancer characterization of GIE prevalence across six immune escap...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Nature Publishing Group US
2023
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181939/ https://www.ncbi.nlm.nih.gov/pubmed/37165135 http://dx.doi.org/10.1038/s41588-023-01367-1 |
_version_ | 1785041683268763648 |
---|---|
author | Martínez-Jiménez, Francisco Priestley, Peter Shale, Charles Baber, Jonathan Rozemuller, Erik Cuppen, Edwin |
author_facet | Martínez-Jiménez, Francisco Priestley, Peter Shale, Charles Baber, Jonathan Rozemuller, Erik Cuppen, Edwin |
author_sort | Martínez-Jiménez, Francisco |
collection | PubMed |
description | Studies have characterized the immune escape landscape across primary tumors. However, whether late-stage metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. We performed a pan-cancer characterization of GIE prevalence across six immune escape pathways in 6,319 uniformly processed tumor samples. To address the complexity of the HLA-I locus in the germline and in tumors, we developed LILAC, an open-source integrative framework. One in four tumors harbors GIE alterations, with high mechanistic and frequency variability across cancer types. GIE prevalence is generally consistent between primary and metastatic tumors. We reveal that GIE alterations are selected for in tumor evolution and focal loss of heterozygosity of HLA-I tends to eliminate the HLA allele, presenting the largest neoepitope repertoire. Finally, high mutational burden tumors showed a tendency toward focal loss of heterozygosity of HLA-I as the immune evasion mechanism, whereas, in hypermutated tumors, other immune evasion strategies prevail. |
format | Online Article Text |
id | pubmed-10181939 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | Nature Publishing Group US |
record_format | MEDLINE/PubMed |
spelling | pubmed-101819392023-05-14 Genetic immune escape landscape in primary and metastatic cancer Martínez-Jiménez, Francisco Priestley, Peter Shale, Charles Baber, Jonathan Rozemuller, Erik Cuppen, Edwin Nat Genet Article Studies have characterized the immune escape landscape across primary tumors. However, whether late-stage metastatic tumors present differences in genetic immune escape (GIE) prevalence and dynamics remains unclear. We performed a pan-cancer characterization of GIE prevalence across six immune escape pathways in 6,319 uniformly processed tumor samples. To address the complexity of the HLA-I locus in the germline and in tumors, we developed LILAC, an open-source integrative framework. One in four tumors harbors GIE alterations, with high mechanistic and frequency variability across cancer types. GIE prevalence is generally consistent between primary and metastatic tumors. We reveal that GIE alterations are selected for in tumor evolution and focal loss of heterozygosity of HLA-I tends to eliminate the HLA allele, presenting the largest neoepitope repertoire. Finally, high mutational burden tumors showed a tendency toward focal loss of heterozygosity of HLA-I as the immune evasion mechanism, whereas, in hypermutated tumors, other immune evasion strategies prevail. Nature Publishing Group US 2023-05-10 2023 /pmc/articles/PMC10181939/ /pubmed/37165135 http://dx.doi.org/10.1038/s41588-023-01367-1 Text en © The Author(s) 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Article Martínez-Jiménez, Francisco Priestley, Peter Shale, Charles Baber, Jonathan Rozemuller, Erik Cuppen, Edwin Genetic immune escape landscape in primary and metastatic cancer |
title | Genetic immune escape landscape in primary and metastatic cancer |
title_full | Genetic immune escape landscape in primary and metastatic cancer |
title_fullStr | Genetic immune escape landscape in primary and metastatic cancer |
title_full_unstemmed | Genetic immune escape landscape in primary and metastatic cancer |
title_short | Genetic immune escape landscape in primary and metastatic cancer |
title_sort | genetic immune escape landscape in primary and metastatic cancer |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10181939/ https://www.ncbi.nlm.nih.gov/pubmed/37165135 http://dx.doi.org/10.1038/s41588-023-01367-1 |
work_keys_str_mv | AT martinezjimenezfrancisco geneticimmuneescapelandscapeinprimaryandmetastaticcancer AT priestleypeter geneticimmuneescapelandscapeinprimaryandmetastaticcancer AT shalecharles geneticimmuneescapelandscapeinprimaryandmetastaticcancer AT baberjonathan geneticimmuneescapelandscapeinprimaryandmetastaticcancer AT rozemullererik geneticimmuneescapelandscapeinprimaryandmetastaticcancer AT cuppenedwin geneticimmuneescapelandscapeinprimaryandmetastaticcancer |