NK cell-mediated cytotoxicity contributes to tumor control by a cytostatic drug combination.
Science
; 362(6421): 1416-1422, 2018 12 21.
Article
en En
| MEDLINE
| ID: mdl-30573629
ABSTRACT
Molecularly targeted therapies aim to obstruct cell autonomous programs required for tumor growth. We show that mitogen-activated protein kinase (MAPK) and cyclin-dependent kinase 4/6 inhibitors act in combination to suppress the proliferation of KRAS-mutant lung cancer cells while simultaneously provoking a natural killer (NK) cell surveillance program leading to tumor cell death. The drug combination, but neither agent alone, promotes retinoblastoma (RB) protein-mediated cellular senescence and activation of the immunomodulatory senescence-associated secretory phenotype (SASP). SASP components tumor necrosis factor-α and intercellular adhesion molecule-1 are required for NK cell surveillance of drug-treated tumor cells, which contributes to tumor regressions and prolonged survival in a KRAS-mutant lung cancer mouse model. Therefore, molecularly targeted agents capable of inducing senescence can produce tumor control through non-cell autonomous mechanisms involving NK cell surveillance.
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Células Asesinas Naturales
/
Protocolos de Quimioterapia Combinada Antineoplásica
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Citotoxicidad Inmunológica
/
Quinasa 4 Dependiente de la Ciclina
/
Quinasa 6 Dependiente de la Ciclina
/
Citostáticos
/
Vigilancia Inmunológica
/
Neoplasias Pulmonares
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Science
Año:
2018
Tipo del documento:
Article
País de afiliación:
Estados Unidos