Regulatory T cell control of systemic immunity and immunotherapy response in liver metastasis.
Sci Immunol
; 5(52)2020 10 02.
Article
en En
| MEDLINE
| ID: mdl-33008914
ABSTRACT
Patients with cancer with liver metastasis demonstrate significantly worse outcomes than those without liver metastasis when treated with anti-PD-1 immunotherapy. The mechanism of liver metastases-induced reduction in systemic antitumor immunity is unclear. Using a dual-tumor immunocompetent mouse model, we found that the immune response to tumor antigen presence within the liver led to the systemic suppression of antitumor immunity. The immune suppression was antigen specific and associated with the coordinated activation of regulatory T cells (Tregs) and modulation of intratumoral CD11b+ monocytes. The dysfunctional immune state could not be reversed by anti-PD-1 monotherapy unless Treg cells were depleted (anti-CTLA-4) or destabilized (EZH2 inhibitor). Thus, this study provides a mechanistic understanding and rationale for adding Treg and CD11b+ monocyte targeting agents in combination with anti-PD-1 to treat patients with cancer with liver metastasis.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Contexto en salud:
1_ASSA2030
/
6_ODS3_enfermedades_notrasmisibles
Problema de salud:
1_doencas_nao_transmissiveis
/
6_digestive_diseases
/
6_liver_cancer
Asunto principal:
Protocolos de Quimioterapia Combinada Antineoplásica
/
Linfocitos T Reguladores
/
Escape del Tumor
/
Inhibidores de Puntos de Control Inmunológico
/
Neoplasias Hepáticas
Límite:
Animals
/
Female
/
Humans
/
Male
Idioma:
En
Revista:
Sci Immunol
Año:
2020
Tipo del documento:
Article