Neoantigen immunogenicity landscapes and evolution of tumor ecosystems during immunotherapy with nivolumab.
Journal
Nature medicine
ISSN: 1546-170X
Titre abrégé: Nat Med
Pays: United States
ID NLM: 9502015
Informations de publication
Date de publication:
30 Sep 2024
30 Sep 2024
Historique:
received:
07
11
2023
accepted:
08
08
2024
medline:
1
10
2024
pubmed:
1
10
2024
entrez:
30
9
2024
Statut:
aheadofprint
Résumé
Neoantigen immunoediting drives immune checkpoint blockade efficacy, yet the molecular features of neoantigens and how neoantigen immunogenicity shapes treatment response remain poorly understood. To address these questions, 80 patients with non-small cell lung cancer were enrolled in the biomarker cohort of CheckMate 153 (CA209-153), which collected radiographic guided biopsy samples before treatment and during treatment with nivolumab. Early loss of mutations and neoantigens during therapy are both associated with clinical benefit. We examined 1,453 candidate neoantigens, including many of which that had reduced cancer cell fraction after treatment with nivolumab, and identified 196 neopeptides that were recognized by T cells. Mapping these neoantigens to clonal dynamics, evolutionary trajectories and clinical response revealed a strong selection against immunogenic neoantigen-harboring clones. We identified position-specific amino acid and physiochemical features related to immunogenicity and developed an immunogenicity score. Nivolumab-induced microenvironmental evolution in non-small cell lung cancer shared some similarities with melanoma, yet critical differences were apparent. This study provides unprecedented molecular portraits of neoantigen landscapes underlying nivolumab's mechanism of action.
Identifiants
pubmed: 39349627
doi: 10.1038/s41591-024-03240-y
pii: 10.1038/s41591-024-03240-y
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : NCI NIH HHS
ID : R01 CA205426
Pays : United States
Organisme : NCI NIH HHS
ID : R35 CA232097
Pays : United States
Informations de copyright
© 2024. The Author(s), under exclusive licence to Springer Nature America, Inc.
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