Genetic immune escape landscape in primary and metastatic cancer.
Journal
Nature genetics
ISSN: 1546-1718
Titre abrégé: Nat Genet
Pays: United States
ID NLM: 9216904
Informations de publication
Date de publication:
05 2023
05 2023
Historique:
received:
28
06
2022
accepted:
10
03
2023
medline:
15
5
2023
pubmed:
11
5
2023
entrez:
10
5
2023
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 37165135
doi: 10.1038/s41588-023-01367-1
pii: 10.1038/s41588-023-01367-1
pmc: PMC10181939
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
820-831Subventions
Organisme : Cancer Research UK
Pays : United Kingdom
Commentaires et corrections
Type : CommentIn
Type : CommentIn
Informations de copyright
© 2023. The Author(s).
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