Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer.
Science
; 348(6230): 124-8, 2015 Apr 03.
Article
en En
| MEDLINE
| ID: mdl-25765070
ABSTRACT
Immune checkpoint inhibitors, which unleash a patient's own T cells to kill tumors, are revolutionizing cancer treatment. To unravel the genomic determinants of response to this therapy, we used whole-exome sequencing of non-small cell lung cancers treated with pembrolizumab, an antibody targeting programmed cell death-1 (PD-1). In two independent cohorts, higher nonsynonymous mutation burden in tumors was associated with improved objective response, durable clinical benefit, and progression-free survival. Efficacy also correlated with the molecular smoking signature, higher neoantigen burden, and DNA repair pathway mutations; each factor was also associated with mutation burden. In one responder, neoantigen-specific CD8+ T cell responses paralleled tumor regression, suggesting that anti-PD-1 therapy enhances neoantigen-specific T cell reactivity. Our results suggest that the genomic landscape of lung cancers shapes response to anti-PD-1 therapy.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Carcinoma de Pulmón de Células no Pequeñas
/
Resistencia a Antineoplásicos
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Anticuerpos Monoclonales Humanizados
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Receptor de Muerte Celular Programada 1
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Neoplasias Pulmonares
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Antineoplásicos
Tipo de estudio:
Diagnostic_studies
/
Etiology_studies
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Incidence_studies
/
Observational_studies
/
Risk_factors_studies
Límite:
Humans
Idioma:
En
Revista:
Science
Año:
2015
Tipo del documento:
Article
País de afiliación:
Estados Unidos