Immune checkpoint blockade reprograms systemic immune landscape and tumor microenvironment in obesity-associated breast cancer.
Cell Rep
; 35(12): 109285, 2021 06 22.
Article
en En
| MEDLINE
| ID: mdl-34161764
ABSTRACT
Immune checkpoint blockade (ICB) has improved outcomes in some cancers. A major limitation of ICB is that most patients fail to respond, which is partly attributable to immunosuppression. Obesity appears to improve immune checkpoint therapies in some cancers, but impacts on breast cancer (BC) remain unknown. In lean and obese mice, tumor progression and immune reprogramming were quantified in BC tumors treated with anti-programmed death-1 (PD-1) or control. Obesity augments tumor incidence and progression. Anti-PD-1 induces regression in lean mice and potently abrogates progression in obese mice. BC primes systemic immunity to be highly responsive to obesity, leading to greater immunosuppression, which may explain greater anti-PD-1 efficacy. Anti-PD-1 significantly reinvigorates antitumor immunity despite persistent obesity. Laminin subunit beta-2 (Lamb2), downregulated by anti-PD-1, significantly predicts patient survival. Lastly, a microbial signature associated with anti-PD-1 efficacy is identified. Thus, anti-PD-1 is highly efficacious in obese mice by reinvigorating durable antitumor immunity. VIDEO ABSTRACT.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Neoplasias de la Mama
/
Microambiente Tumoral
/
Inhibidores de Puntos de Control Inmunológico
/
Obesidad
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Cell Rep
Año:
2021
Tipo del documento:
Article
País de afiliación:
Estados Unidos